Exosomes derived from cancer-associated fibroblasts (CAFs) can affect tumor microenvironment (TME) of thyroid cancer (TC). The cAMP response element binding protein 1 (CREB1) acts as a transcription factor to participate in cancer development. Currently, we aimed to explore the molecular mechanism of exosome-associated CREB1 and C-C motif chemokine ligand 20 (CCL20) in TC.

The mRNA and protein levels were examined via RT-qPCR and western blot. Gene interaction was analyzed using ChIP and dual-luciferase reporter assays. Cell migration, invasion and proliferation were assessed by wound healing, transwell and EdU assays. Exosomes were characterized by morphology observation and western blot. The proliferation and apoptosis of CD8+ T cells were detected by immunofluorescence and flow cytometry. In vivo assays were performed by establishing xenograft models.

CREB1 was highly expressed in TC. CREB1 positively interacted with CCL20 in TC. CREB1 facilitated TC cell migration, invasion and proliferation via targeting CCL20. CCL20 expression was reduced by transferring CAFs-secreted exosomes sheltering CREB1 downregulation. Exosomal CREB1 knockdown receded cell progression and enhanced CD8+ T function by mediating CCL20. CAFs-associated exosomal CREB1 downregulation inhibited tumorigenesis through affecting CCL20.

CAFs-derived exosomes accelerated the malignant behaviors and immune evasion in TC by carrying CREB1 to up-regulate CCL20.

Melanoma, an aggressive form of skin cancer, presents significant therapeutic challenges due to its resistance to conventional treatments and propensity for metastasis. Exosomes, nanoscale vesicles secreted by a wide variety of cells, have emerged as promising tools for developing novel melanoma therapies. Exosome-based therapeutic approaches offer several advantages, including inherent biocompatibility, low immunogenicity, and the ability to cross biological barriers. This review explores the therapeutic potential of exosomes in melanoma treatment, focusing on their multifaceted roles in modulating tumor cell behavior, enhancing anti-tumor immune responses, and serving as targeted drug delivery vehicles. We discuss various strategies employed to engineer exosomes for enhanced therapeutic efficacy, including loading them with chemotherapeutic agents, small interfering RNAs (siRNAs), microRNAs (miRNAs), and immunomodulatory molecules. Additionally, we highlight the potential of exosomes derived from diverse sources to enhance anti-cancer effects. Furthermore, we address the challenges and future directions in translating exosome-based therapies from bench to bedside, emphasizing the need for standardized isolation and manufacturing protocols, as well as rigorous preclinical and clinical evaluations to unlock the full therapeutic potential of exosomes in the fight against melanoma.

Abnormal metabolism is a characteristic of malignant tumors. Numerous factors play roles in the regulation of tumor metabolism. As epigenetic regulators, enhancers, especially the super-enhancers (SEs), serve as platforms for transcription factors that regulate the expression of metabolism-related enzymes or transporters at the gene level. In this study, we review the effects of enhancer/ SE-driven genes on tumor metabolism and immunity. Enhancers/SEs play regulatory roles in glucose metabolism (glycolysis, gluconeogenesis, tricarboxylic acid (TCA) cycle, pyruvate, and pentose phosphate pathway, lipid metabolism (cholesterol, fatty acid, phosphatide, and sphingolipid), and amino acid metabolism (glutamine, tryptophan, arginine, and cystine). By regulating tumor metabolism, enhancers and SEs can reprogram tumor microenvironment, especially the status of various immune cells. Therefore, interfering enhancers/SEs that regulate the tumor metabolism is likely to enhance the effectiveness of immunotherapy.

High-grade gliomas (HGGs), including glioblastoma (GBM) in adults and diffuse intrinsic pontine glioma (DIPG) in children, are among the most aggressive and deadly brain tumors. A key factor in their resilience is the presence of glioma stem cells (GSCs), which drive tumor initiation, progression, and resistance to treatment. Targeting and eradicating GSCs holds potential for curing both GBM and DIPG. Natural killer (NK) cells, as part of the innate immune system, naturally recognize and destroy malignant cells. Recent advances in NK cell-based therapies, such as chimeric antigen receptor (CAR)-NK cells, NK cell engagers, and NK cell-derived exosomes, offer promising approaches for treating GBM and DIPG, particularly by addressing the persistence of GSCs. This review highlights these advancements, explores challenges such as the blood-brain barrier and the immunosuppressive tumor microenvironment, and proposes future directions for improving and clinically advancing these NK cell-based therapies for HGGs.

Natural killer (NK) cell-derived exosomes (NK-Exos) are emerging as a promising avenue in cancer immunotherapy due to their inherent tumor-targeting properties and their capacity to deliver therapeutic agents directly to malignant cells. This research delves into the boosted anti-tumor potency of NK-Exos that has been genetically enhanced to overexpress NKG2D, a vital activating receptor, along with interleukin-24 (IL24), a cytokine renowned for its selective suppressive impact on tumor cells. NKG2D facilitates the recognition of tumor cells by binding to stress-induced ligands, while IL24 induces apoptosis and modulates immune responses to enhance tumor destruction. The NK-Exos engineered to express both NKG2D and IL24 significantly enhanced tumor targeting and increased the apoptosis rate of tumor cells by 30% in A549 and by 20% in HELA at 48 h compared with non-modified NK-Exos, respectively. Furthermore, this enhancement also impacted cell proliferation, with inhibition rates increasing by 30%, 15%, and 15% in A549, HELA, and MCF-7 cells, respectively, and it reduced A549 cell migration by 10%. The integration of NKG2D and IL24 within NK-Exos confers a dual therapeutic mechanism, synergistically amplifying their efficacy in cancer treatment. The utility of NK-Exos co-expressing NKG2D and IL24 offers a novel approach to overcome the limitations of current therapies, providing prolonged tumor suppression and precise targeting of malignant cells and holding great promise for clinical application.

This article reviews plant-derived exosome-like nanoparticles (ELNs), and highlights their potential in regenerative medicine. Various extraction techniques, including ultracentrifugation and ultrafiltration, and their impact on ELN purity and yield were discussed. Characterization methods such as microscopy and particle analysis are found to play crucial roles in defining ELN properties. This review is focused on exploring the therapeutic potential of ELNs in tissue repair, immune regulation, and antioxidant activities. Further research and optimization methods for extraction of ELNs to realize clinical potential applications are necessary.

During this era of rapid advancements in cancer immunotherapy, the application of cell-released small vesicles that activate the immune system is of considerable interest. Exosomes are cell-derived nanovesicles that show great promise for the immunological treatment of cancer because of their immunogenicity and molecular transfer capacity. Recent technological advancements have enabled the identification of functional functions that exosome cargoes perform in controlling immune responses. Exosomes are originated specifically from immune cells and tumor cells and they show unique composition patterns directly related to the immunotherapy against cancer. Exosomes can also deliver their cargo to particular cells, which can affect the phenotypic and immune-regulatory functions of those cells. Exosomes can influence the course of cancer and have therapeutic benefits by taking part in several cellular processes; as a result, they have the dual properties of activating and restraining cancer. Exosomes have tremendous potential for cancer immunotherapy; they may develop into the most powerful cancer vaccines and carriers of targeted antigens and drugs. Comprehending the potential applications of exosomes in immune therapy is significant for regulating cancer progression. This review offers an analysis of the function of exosomes in immunotherapy, specifically as carriers that function as diagnostic indicators for immunological activation and trigger an anti-cancer immune response. Moreover, it summarizes the fundamental mechanism and possible therapeutic applications of exosome-based immunotherapy for human cancer.

Gastric cancer (GC), particularly in East Asia, is among the most prevalent cancers with high mortality rates. According to recent epidemiological data, patients with GC account for over a quarter of all cancer incidences and approximately one third of cancer-related deaths in East Asia. Liver metastasis (LM) is not only a common form of GC distant metastasis but also poses a major challenge to the prognosis and treatment of patients with advanced GC. Increasing evidence has shown that the gut-liver axis plays a pivotal role in maintaining the stomach-liver-gut homeostasis. Exosomes are small secreted vesicles enriched with specific proteins, lipids, and nucleic acids. These vesicles exhibit significant activities in signal transmission to adjacent or distant cells in the gut-liver axis, as well as in remodeling the tumor microenvironment. Some research have pointed out that exosomes promote LM of various cancers. However, there still lack of complete and systematic review on how exosomes affect GC-LM. In this article, we present a comprehensive description to explore the role of GC-derived exosomes in the occurrence and development of metastatic hepatocellular carcinoma (HCC).

Cytokines play a crucial role in mediating cell communication within the tumor microenvironment (TME). Tumor-associated macrophages are particularly influential in the regulation of immunosuppressive cytokines, thereby supporting tumor metastasis. The upregulation of Th2 cytokines in cancer cells is recognized for its involvement in suppressing anticancer immunity. However, the association between these cytokines and tumor-secreted extracellular vesicles (EVs) remains poorly understood. Therefore, our objective was to investigate the connection between tumor-promoting macrophages and melanoma-derived EVs. The analysis from altered cytokine profile data showed that melanoma-derived EVs upregulate Th2 cytokine expression in naïve macrophages, thereby contributing to the promotion of tumor-supporting functions. Notably, many of these cytokines were also found to be upregulated in metastatic melanoma patients (n = 30) compared to healthy controls (n = 33). Overall, our findings suggest a strong connection between melanoma secretory EVs and the induction of tumor-associated macrophages that facilitates the development of an immunosuppressive TME, supporting melanoma metastasis through regulation at both local and systemic levels.

Ovarian cancer (OC) remains one of the most lethal gynecological malignancies, largely due to its late-stage diagnosis and high recurrence rates. Chronic inflammation is a critical driver of OC progression, contributing to immune evasion, tumor growth, and metastasis. Inflammatory cytokines, including IL-6, TNF-α, and IL-8, as well as key signaling pathways such as nuclear factor kappa B (NF-kB) and signal transducer and activator of transcription 3 (STAT3), are upregulated in OC, promoting a tumor-promoting environment. The tumor microenvironment (TME) is characterized by immune cells like tumor-associated macrophages (TAMs) and regulatory T cells (Tregs), which suppress anti-tumor immune responses, facilitating immune evasion. Furthermore, OC cells utilize immune checkpoint pathways, including PD-1/PD-L1, to inhibit cytotoxic T cell activity. Targeting these inflammatory and immune evasion mechanisms offers promising therapeutic strategies. COX-2 inhibitors, Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway blockers, and NF-kB inhibitors have shown potential in preclinical studies, while immune checkpoint inhibitors targeting PD-1/PD-L1 and CTLA-4 have been explored with mixed results in OC. Additionally, emerging research on the microbiome and inflammation-related biomarkers, such as microRNAs (miRNAs) and exosomes, points to new opportunities for early detection and precision medicine. Future approaches to OC treatment must focus on personalized strategies that target the inflammatory TME, integrating anti-inflammatory therapies with immunotherapy to enhance patient outcomes. Continued research into the interplay between inflammation and immune evasion in OC is essential for developing effective, long-lasting treatments.

Nasopharyngeal carcinoma (NPC) is a malignancy arising from the epithelium of the nasopharynx. Given its late diagnosis, NPC raises serious considerations in Southeast Asia. In addition to resistance to conventional treatment that combines chemotherapy and radiation, NPC has high rates of metastasis and frequent recurrence. Exosomes are small membrane vesicles at the nanoscale that transport physiologically active compounds from their source cell and have a crucial function in signal transmission and intercellular message exchange. The exosomes detected in the tissues of NPC patients have recently emerged as a potential non-invasive liquid biopsy biomarker that plays a role in controlling the tumor pathophysiology. Here, we take a look back at what we know so far about the complex double-edged sword role of exosomes in NPC. Exosomes could serve as biomarkers and therapeutic agents, as well as the molecular mechanisms by which they promote cell growth, angiogenesis, metastasis, immunosuppression, radiation resistance, and chemotherapy resistance in NPC. Furthermore, we go over some of the difficulties and restrictions associated with exosome use. It is anticipated that this article would provide the reference for the apply of exosomes in clinical practice.

Exosomes, extracellular vesicles originating from endosomes, were discovered in the late 1980s and their function in intercellular communication has since garnered considerable interest. Exosomes are lipid bilayer-coated vesicles that range in size from 30 to 150 nm and appear as sacs under the electron microscope. Exosome secretion is crucial for cell-to-cell contact in both normal physiology and the development and spread of tumors. Furthermore, cancer cells can secrete more exosomes than normal cells. Scientists believe that intercellular communication in the complex tissue environment of the human body is an important reason for cancer cell invasion and metastasis. For example, some particles containing regulatory molecules are secreted in the tumor microenvironment, including exosomes. Then the contents of exosomes can be released by donor cells into the environment and interact with recipient cells to promote the migration and invasion of tumor cells. Therefore, in this review, we summarized the biogenesis of exosome, as well as exosome cargo and related roles. More importantly, this review introduces and discusses the factors that have been reported to affect exosome secretion in tumors and highlights the important role of exosomes in tumors.

Tumor vaccines, as an immunotherapeutic approach, harness the body's immune cells to provoke antitumor responses, which have shown promising efficacy in clinical settings. However, the immunosuppressive tumor microenvironment (TME) and the ineffective vaccine delivery systems hinder the progression of many vaccines beyond phase II trials. This article begins with a comprehensive review of the complex interactions between tumor vaccines and TME, summarizing the current state of vaccine clinical research. Subsequently, we review recent advancements in targeted vaccine delivery systems and explore biomaterial-based tumor vaccines as a strategy to improve the efficacy of both delivery systems and treatment. Finally, we have presented our perspectives on tumor vaccine development, aiming to advance the field towards the creation of more effective tumor vaccines.

Exosomal microRNAs (exomiRs) play a critical role in intercellular communication, especially in cancer, where they regulate key cellular processes like proliferation, angiogenesis, and metastasis, highlighting their significance as potential diagnostic and therapeutic targets. Here, we aimed to characterize the role of exomiRs, derived from seven cancer types (four cell lines and three tumors), in influencing the pre-metastatic niche (PMN). In each cancer type we extracted high confidence exomiRs (LogFC >= 2 in exosomes relative to control), their experimentally validated targets, and the enriched pathways among those targets. We then selected the top100 high-confidence targets based on their frequency of appearance in the enriched pathways. We observed significantly higher GC content in exomiRs relative to genomic background. Gene Ontology analysis revealed both general cancer processes, such as wound healing and epithelial cell proliferation, as well as cancer-specific processes, such as "angiogenesis" in the kidney and "ossification" in the lung. ExomiR targets were enriched for cancer-specific tumor suppressor genes and downregulated in PMN formed in lungs compared to normal. Motif analysis showed high inter-cancer similarity among motifs enriched in exomiRs. Our analysis recapitulated exomiRs associated with M2 macrophage differentiation and chemoresistance, such as miR-21 and miR-222-3p, regulating signaling pathways like PTEN/PI3/Akt, NF-kB, etc. Additionally, Cox regression analysis in TCGA indicated that exomiR targets are significantly associated with better overall survival of patients. Lastly, support vector machine model using exomiR targets gene expression classified responders and non-responders to therapy with an AUROC ranging from 0.72 to 0.96, higher than previously reported gene signatures.

Gastric cancer (GC) represents a prevalent malignancy globally, often diagnosed at advanced stages owing to subtle early symptoms, resulting in a poor prognosis. Exosomes are extracellular nano-sized vesicles and are secreted by various cells. Mounting evidence indicates that exosomes contain a wide range of molecules, such as DNA, RNA, lipids, and proteins, and play crucial roles in multiple cancers including GC. Recently, with the rapid development of mass spectrometry-based detection technology, researchers have paid increasing attention to exosomal cargo proteins. In this review, we discussed the origin of exosomes and the diagnostic and prognostic roles of exosomal proteins in GC. Moreover, we summarized the biological functions of exosomal proteins in GC processes, such as proliferation, metastasis, drug resistance, stemness, immune response, angiogenesis, and traditional Chinese medicine therapy. In summary, this review synthesizes current advancements in exosomal proteins associated with GC, offering insights that could pave the way for novel diagnostic and therapeutic strategies for GC in the foreseeable future.

Cancer immunotherapy uses the body's immune system to combat cancer, marking a significant advancement in treatment. This review traces its evolution from the late 19th century to its current status. It began with William Coley's pioneering work using bacterial toxins to stimulate the immune system against cancer cells, establishing the foundational concept of immunotherapy. In the mid-20th century, cytokine therapies like interferons and interleukins emerged, demonstrating that altering the immune response could reduce tumors and highlighting the complex interplay between cancer and the immune system. The discovery of immune checkpoints, regulatory pathways that prevent autoimmunity but are exploited by cancer cells to evade detection, was a pivotal development. Another major breakthrough is CAR-T cell therapy, which involves modifying a patient's T cells to target cancer-specific antigens. This personalized treatment has shown remarkable success in certain blood cancers. Additionally, cancer vaccines aim to trigger immune responses against tumor-specific or associated antigens, and while challenging, ongoing research is improving their efficacy. The historical progression of cancer immunotherapy, from Coley's toxins to modern innovations like checkpoint inhibitors and CAR-T cell therapy, underscores its transformative impact on cancer treatment. As research delves deeper into the immune system's complexities, immunotherapy is poised to become even more crucial in oncology, offering renewed hope to patients globally.

Exosomes, a subset of extracellular vesicles (EVs), have emerged as crucial players in prostate cancer (PCa) diagnosis. It is involved in cell-to-cell communication. Exosomes cargo based tumor microenvironment (TME) cellular communication is a secret of cancer development and progression. PCa, the second most common cancer in men, holds early diagnostic challenges due to a lack of specific biomarkers. Recent studies have found that tumor-derived exosomes (TEXs) contribute to PCa progression by facilitating immune suppression, angiogenesis, and metastasis. These exosomes, detectable in serum, plasma, and urine, carry diagnostic biomarkers such as specific miRNAs and proteins. Urine-derived exosomes, with their distinct miRNAs, provide a non-invasive diagnostic tool. This method becomes cutting-edge liquid biopsy in PCa. Advanced techniques, such as including AI and nanoplatform-based sensors, improve the precision of exosome-based PCa diagnostics, offering enhanced detection and better treatment outcomes.

An immunosuppressive tumour microenvironment strongly influences response rates in patients receiving immune checkpoint blockade-based cancer immunotherapies, such as programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1). Here we demonstrate that metal-ion-chelating L-phenylalanine nanostructures synergize with short-term starvation (STS) to remodel the immunosuppressive microenvironment of breast and colorectal tumours. These nanostructures modulate the electrophysiological behaviour of dendritic cells and activate them through the NLRP3 inflammasome and calcium-mediated nuclear factor-κB pathway. STS promotes the cellular uptake of nanostructures through amino acid transporters and plays a key role in dendritic cell maturation and tumour-specific cytotoxic T lymphocyte responses. This study demonstrates the potential role of metal-ion-chelating L-phenylalanine nanostructures in activating immune responses and the effect of STS treatment in improving nanomaterial-mediated cancer immunotherapy.

Pulsed electromagnetic field (PEMF) therapy is a potential non-invasive treatment to modulate immune responses and inhibit tumor growth. Cervical cancer (CC) is influenced by IL-37-mediated immune regulation, making PEMF therapy a potential strategy to impede CC progression. This study aimed to elucidate the effects of PEMF on IL-37 regulation and its molecular mechanisms in CC. CC cell-xenografted mouse models, including IL-37 transgenic (IL-37tg) mice, were used to assess tumor growth through in vivo fluorescence imaging and analyze CC cell apoptosis via flow cytometry. TCGA-CESC transcriptome and clinical data were analyzed to identify key inflammation and immune-related genes. CD8+ T cell models were stimulated with PEMF, and apoptosis, oxidative stress, and inflammatory factor expression were analyzed through RT-qPCR, Western blot, and flow cytometry. PEMF treatment significantly inhibited IL-37 expression (p < 0.05), promoted inflammatory factor release (TNF-α and IL-6), and activated oxidative stress, leading to increased CC cell apoptosis (p < 0.05). IL-37 interaction with SMAD3 impacted the p38/NF-κB signaling pathway, modulating CD8+ T cell activity and cytotoxicity. Co-culture of Hela cells with CD8+ T cells under PEMF treatment showed reduced proliferation (by 40%), migration, and invasion (p < 0.05). In vivo experiments with CC-bearing mice demonstrated that PEMF treatment downregulated IL-37 expression (p < 0.05), enhanced CD8+ T cell function, and inhibited tumor growth (p < 0.05). These molecular mechanisms were validated through RT-qPCR, Western blot, and immunohistochemistry. Thus, PEMF therapy inhibits CC progression by downregulating IL-37 and improving CD8+ T cell function via the SMAD3/p38/NF-κB signaling pathway.

The phenotypic characteristics and meat quality of skeletal muscles are collectively determined by muscle cells and their intricate interactions with the extracellular microenvironment. In this study, we evaluated muscle fiber phenotypes in the longissimus dorsi (HC-L) and psoas major (HC-P) of Hechuan black pigs. The results revealed significant differences in muscle fiber diameter, density, and type (P < 0.05). Subsequently, co-culture experiments with myoblasts demonstrated that skeletal muscle-derived exosomes (SKM-Exos) promoted myoblast proliferation and differentiation with P-Exo exhibiting superior efficacy in promoting the augmentation of MyHCIIa fiber. Furthermore, SKM-Exos are inherently heterogeneous, and the microRNAs (miRNAs) present in SKM-Exos are selectively coated. Notably, the expression of miR-4331-3p was significantly higher in SKM-Exos than in the corresponding skeletal muscles. The expression of miR-4331-3p was significantly elevated in the SKM-Exos of HC-L compared to that of HC-P, and it interacted with differentially expressed genes between HC-L and HC-P. Moreover, miR-4331-3p enhanced myoblast proliferation and inhibited differentiation. Our findings offer valuable insights into the molecular processes that contribute to meat formation, including intricate cellular interactions.

Exosomes are widely recognized for their roles in numerous biological processes and as intercellular communication mediators. Human cancerous and normal cells can both produce massive amounts of exosomes. They are extensively dispersed in tumor-modeling animals' pleural effusions, ascites, and plasma from people with cancer. Tumor cells interact with host cells by releasing exosomes, which allow them to interchange various biological components. Tumor growth, invasion, metastasis, and even tumorigenesis can all be facilitated by this delicate and complex system by modifying the nearby and remote surroundings. Due to the existence of significant levels of biomolecules like microRNA, exosomes can modulate the immune system's stimulation or repression, which in turn controls tumor growth. However, the role of microRNA in exosome-mediated communication between immunological and cancer cells is still poorly understood. This study aims to get the most recent information on the "yin and yang" of exosomal microRNA in the regulation of tumor immunity and immunotherapy, which will aid current cancer treatment and diagnostic techniques.

Exosomes, which are extracellular vesicles with a diameter ranging from 40 to 160 nm, are abundantly present in various body fluids. Exosomal microRNA (ex-miR), due to its exceptional sensitivity and specificity, has garnered significant attention. Notably, ex-miR is consistently detected in almost all bodily fluids, highlighting its potential as a reliable biomarker. This attribute of ex-miR has piqued considerable interest in its application as a diagnostic tool for the early detection, continuous monitoring, and prognosis evaluation of cancer. Given the critical role of exosomes and their cargo in cancer biology, this review explores the intricate processes of exosome biogenesis and uptake, their multifaceted roles in cancer development and progression, and the potential of ex-miRs as biomarkers for tumor diagnosis and prognosis.

Lung cancer is frequently detected in an advanced stage and has an unfavourable prognosis. Conventional therapies are ineffective for the treatment of metastatic lung cancer. While certain molecular targets have been identified as having a positive response, the absence of appropriate drug carriers prevents their effective utilization. Lung cancer cell-derived exosomes (LCCDEs) have gained attention for their involvement in the development of cancer, as well as their potential for use in diagnosing, treating, and predicting the outcome of lung cancer. This is due to their biological roles and their inherent ability to transport biomolecules from the donor cells. Lung cancer-associated cell-derived extracellular vesicles (LCCDEVs) have the ability to enhance cell proliferation and metastasis, influence angiogenesis, regulate immune responses against tumours during the development of lung cancer, control drug resistance in lung cancer treatment, and are increasingly recognised as a crucial element in liquid biopsy evaluations for the detection of lung cancer. Therapeutic exosomes, which possess inherent intercellular communication capabilities, are increasingly recognised as effective vehicles for targeted drug delivery in precision medicine for tumours. This is due to their exceptional biocompatibility, minimal immunogenicity, low toxicity, prolonged circulation in the bloodstream, biodegradability, and ability to traverse different biological barriers. Currently, multiple studies are being conducted to create new means of diagnosing and predicting outcomes using LCCDEs, as well as to develop techniques for utilizing exosomes as effective carriers for medication delivery. This paper provides an overview of the current state of lung cancer and the wide range of applications of LCCDEs. The encouraging findings and technologies suggest that the utilization of LCCDEs holds promise for the clinical treatment of lung cancer patients.

Anthracyclines belong to a class of anti-tumor antibiotics, and their severe cardiotoxicity significantly limits their clinical use. Exosomes play key roles in intercellular communication, characterized by high biocompatibility and specific tissue and organ homing effects. In this study, doxorubicin, an anthracycline anticancer drug widely used in clinical chemotherapy, was selected as a model drug. To address the significant cardiotoxicity associated with doxorubicin, tumor exosomes are utilized as drug carriers. The homing effect of autologous exosomes enhances drug uptake by tumor cells and reduces cardiotoxicity. To enhance the stability of exosomes, improve therapeutic effectiveness, and reduce toxic side effects, chitosan was utilized to modify the surface of exosomes. Chitosan has a specific anti-tumor effect because it can target the CD44 receptor of tumor stem cells and interact with tumor cells through charge adsorption. Through in vitro cell experiments, in vivo pharmacokinetic experiments, and an in situ ectopic nude mouse tumor model, the study demonstrated that chitosan-modified tumor exosomes significantly alleviated the severe cardiotoxicity of doxorubicin, while also showing remarkable anti-tumor efficacy. This study introduces a novel approach to reduce the adverse side effects of anthracycline chemotherapeutic drugs and presents a highly promising nanocarrier delivery system.

Over the past decades, cancer immunotherapy has encountered challenges such as immunogenicity, inefficiency, and cytotoxicity. Consequently, exosome-based cancer immunotherapy has gained rapid traction as a promising alternative. Exosomes, a type of extracellular vesicles (EVs) ranging from 50 to 150 nm, are self-originating and exhibit fewer side effects compared to traditional therapies. Exosome-based immunotherapy encompasses three significant areas: cancer vaccination, co-inhibitory checkpoints, and adoptive T-cell therapy. Each of these fields leverages the inherent advantages of exosomes, demonstrating substantial potential for individualized tumor therapy and precision medicine. This review aims to elucidate the reasons behind the promise of exosome-based nanoparticles as cancer therapies by examining their characteristics and summarizing the latest research advancements in cancer immunotherapy.

Oral cancer, a malignancy that is prevalent worldwide, is often diagnosed at an advanced stage. MicroRNAs (miRNAs) in circulating exosomes have emerged as promising cancer biomarkers. The role of miRNA let-7c-5p in oral cancer remains underexplored, and its potential involvement in tumorigenesis warrants comprehensive investigation.

Serum samples from 30 patients with oral cancer and 20 healthy controls were used to isolate exosomes and quantify their RNA content. Isolation of the exosomes was confirmed through transmission electron microscopy. Quantitative PCR was used to assess the miRNA profiles. The effects of let-7c-5p and TAGLN overexpression on oral cancer cell viability, migration, and invasion were analyzed via CCK-8 and Transwell assays. Moreover, we conducted mRNA sequencing of exosomal RNA from exosomes overexpressing let-7c-5p to delineate the gene expression profile and identify potential let-7c-5p target genes.

let-7c-5p was upregulated in serum-derived exosomes of patients with oral cancer. Overexpression of let-7c-5p in the TCA8113 and CAL-27 cell lines enhanced their proliferative, migratory, and invasive capacities, and overexpression of let-7c-5p cell-derived exosomes promoted oral cancer cell invasiveness. Exosomal mRNA sequencing revealed 2,551 differentially expressed genes between control cell-derived exosomes and overexpressed let-7c-5p cell-derived exosomes. We further identified TAGLN as a direct target of let-7c-5p, which has been implicated in modulating the oncogenic potential of oral cancer cells. Overexpression of TAGLN reverses the promoting role of let-7c-5p on oral cancer cells.

Our findings highlight the role of exosomal let-7c-5p in enhancing oral cancer cell aggressiveness by downregulating TAGLN expression, highlighting its potential as a diagnostic and therapeutic strategy.

Biomarkers that effectively predict response to anti-PD-1 mAb therapy in cancer patients are an unmet need. We evaluated the utility of small extracellular vesicles (sEV) as biomarkers of response to immunotherapy in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients.

Plasma sEV were isolated from 24 R/M HNSCC patients prior to immunotherapy initiation. sEV were separated by immune capture into T cell-derived CD3(+) and tumor-enriched CD3(-) subsets. Stimulatory and suppressive profiles of CD3(-) sEV were determined by on-bead flow cytometry. Differences were assessed using nonparametric tests. Multivariable Cox regression was used to evaluate the relationship with overall (OS) and progression free survival (PFS).

CD3(-)CD44v3(+) sEV represented the majority of plasma sEV; the T-cell-derived CD3(+) fraction was significantly smaller. High CD3(+) sEV was associated with better OS and PFS. Total CD3(-)CD44v3(+) sEV was not associated with outcome. However, suppressive and stimulatory profiles were associated with OS; the suppressive/stimulatory ratio was associated with best response. Exploration of individual proteins on CD3(-) sEV showed that high PD-L1 and high CTLA-4 were associated with better outcomes.

Evaluation of the T cell-derived-CD3(+) and tumor-enriched CD3(-) plasma sEV subsets indicated their potential utility as biomarkers of response to immunotherapy.

Radiotherapy (RT) controls local lesions, meantime it has the capability to induce systemic response to inhibit distant, metastatic, non-radiated tumors, which is referred to as the "abscopal effect". It is widely recognized that radiotherapy can stimulate systemic immune response. This provides a compelling theoretical basis for the combination of immune therapy combined with radiotherapy(iRT). Indeed, this phenomenon has also been observed in clinical treatment, bringing significant clinical benefits to patients, and a series of basic studies are underway to amplify this effect. However, the molecular mechanisms of immune response induced by RT, determination of the optimal treatment regimen for iRT, and how to amplify the abscopal effect. In order to amplify and utilize this effect in clinical management, these key issues require to be well addressed; In this review, we comprehensively summarize the growing consensus and emphasize the emerging limitations of enhancing the abscopal effect with radiotherapy or immunotherapy. Finally, we discuss the prospects and barriers to the current clinical translational applications.

Ovarian cancer remains a leading cause of death among gynecological cancers, largely due to its propensity for peritoneal metastasis and the development of drug resistance. This review concentrates on the molecular underpinnings of these two critical challenges. We delve into the role of exosomes, the nano-sized vesicles integral to cellular communication, in orchestrating the complex interactions within the tumor microenvironment that facilitate metastatic spread and thwart therapeutic efforts. Specifically, we explore how exosomes drive peritoneal metastasis by promoting epithelial-mesenchymal transition in peritoneal mesothelial cells, altering the extracellular matrix, and supporting angiogenesis, which collectively enable the dissemination of cancer cells across the peritoneal cavity. Furthermore, we dissect the mechanisms by which exosomes contribute to the emergence of drug resistance, including the sequestration and expulsion of chemotherapeutic agents, the horizontal transfer of drug resistance genes, and the modulation of critical DNA repair and apoptotic pathways. By shedding light on these exosome-mediated processes, we underscore the potential of exosomal pathways as novel therapeutic targets, offering hope for more effective interventions against ovarian cancer's relentless progression.

Exosomes are the primary category of extracellular vesicles (EVs), which are lipid-bilayer vesicles with biological activity spontaneously secreted from either normal or tansformed cells. They serve a crucial role for intercellular communication and affect extracellular environment and the immune system. Tumor-derived exosomes (TEXs) enclose high levels of immunosuppressive proteins, including programmed death-ligand 1 (PD-L1). PD-L1 and its receptor PD-1 act as crucial immune checkpoint molecules, thus facilitating tumor advancement by inhibiting immune responses. PDL-1 is abundantly present on tumor cells and interacts with PD-1 on activated T cells, resulting in T cell suppression and allowing immune evasion of cancer cells. Various FDA-approved monoclonal antibodies inhibiting the PD-1/PD-L1 interaction are commonly used to treat a diverse range of tumors. Although the achieved results are significant, some individuals have a poor reaction to PD-1/PD-L1 blocking. PD-L1-enriched TEXs may mimic the impact of cell-surface PD-L1, consequently potentiating tumor resistance to PD1/PD-L1 based therapy. In light of this, a strong correlation between circulating exosomal PD-L1 levels and response rate to anti-PD-1/PD-L1 antibody treatment has been evinced. This article inspects the function of exosomal PDL-1 in developing resistance to anti-PD-1/PD-L1 therapy for opening new avenues for overcoming tumor resistance to such modalities and development of more favored combination therapy.

Cancer stem cells (CSCs), the master regulators of tumor heterogeneity and progression, exert profound influence on cancer metastasis, via various secretory vesicles. Emerging from CSCs, the exosomes serve as pivotal mediators of intercellular communication within the tumor microenvironment, modulating invasion, angiogenesis, and immune responses. Moreover, CSC-derived exosomes play a central role in sculpting a dynamic landscape, contributing to the malignant phenotype. Amidst several exosomal cargoes, misfolded proteins have recently gained attention for their dual functions in maintaining protein homeostasis and promoting tumor progression. Disrupting these communication pathways could potentially prevent the maintenance and expansion of CSCs, overcome treatment resistance, and inhibit the supportive environment created by the tumor microenvironment, thereby improving the effectiveness of cancer therapies and reducing the risk of tumor recurrence and metastasis. Additionally, exosomes have also shown potential therapeutic applications, such as in drug delivery or as biomarkers for cancer diagnosis and prognosis. Therefore, comprehending the biology of exosomes derived from CSCs is a multifaceted area of research with implications in both basic sciences and clinical applications. This review explores the intricate interplay between exosomal misfolded proteins released by CSCs, the potent contributor in tumor heterogeneity, and their impact on cellular processes, shedding light on their role in cancer progression.

Exosomal microRNAs (exomiRs), transported via exosomes, play a pivotal role in intercellular communication. In cancer, exomiRs influence tumor progression by regulating key cellular processes such as proliferation, angiogenesis, and metastasis. Their role in mediating communication between cancer cells and the tumor microenvironment highlights their significance as potential diagnostic and therapeutic targets.

In this study, we aimed to characterize the role of exomiRs in influencing the pre-metastatic niche (PMN). Across 7 tumor types, including 4 cell lines and three tumors, we extracted high confidence exomiRs (Log FC >= 2 in exosomes relative to control) and their targets (experimentally identified and targeted by at least 2 exomiRs). Subsequently, we identified enriched pathways and selected the top 100 high-confidence exomiR targets based on the frequency of their appearance in the enriched pathways. These top 100 targets were consistently used throughout the analysis.

Cancer cell line and tumor derived ExomiRs have significantly higher GC content relative to genomic background. Pathway enriched among the top exomiR targets included general cancer-associated processes such as "wound healing" and "regulation of epithelial cell proliferation", as well as cancer-specific processes, such as "regulation of angiogenesis in kidney" (KIRC), "ossification" in lung (LUAD), and "positive regulation of cytokine production" in pancreatic cancer (PAAD). Similarly, 'Pathways in cancer' and 'MicroRNAs in cancer' ranked among the top 10 enriched KEGG pathways in all cancer types. ExomiR targets were not only enriched for cancer-specific tumor suppressor genes (TSG) but are also downregulated in pre-metastatic niche formed in lungs compared to normal lung. Motif analysis shows high similarity among motifs identified from exomiRs across cancer types. Our analysis recapitulates exomiRs associated with M2 macrophage differentiation and chemoresistance such as miR-21 and miR-222-3p, regulating signaling pathways such as PTEN/PI3/Akt, NF-κB, etc. Cox regression indicated that exomiR targets are significantly associated with overall survival of patients in TCGA. Lastly, a Support Vector Machine (SVM) model using exomiR target gene expression classified responders and non-responders to neoadjuvant chemotherapy with an AUROC of 0.96 (in LUAD), higher than other previously reported gene signatures.

Our study characterizes the pivotal role of exomiRs in shaping the PMN in diverse cancers, underscoring their diagnostic and therapeutic potential.

In recent years, the cargo profiles of extracellular vesicles (EVs), which were inherited from their parent cells, have emerged as a reliable biomarker for liquid biopsy (LB) in disease diagnosis, prognosis, and treatment monitoring. EVs secreted by different cells exhibit distinct characteristics, particularly in terms of disease diagnosis and prediction. However, currently available techniques for the quantitative analysis of EV cargoes, including enzyme-linked immunosorbent assay (ELISA), cannot specifically identify the cellular origin of EVs, thus seriously affecting the accuracy of EV-based liquid biopsy. In light of this, we here developed ultrabright fluorescent nanosphere (FNs)-based test strips which have the unique capability to specifically assess the levels of PD-L1-positive EVs (PD-L1+ EVs) derived from both tumor cells and immune cells in bodily fluids. The levels of PD-L1+ EV subpopulations in human saliva were quantified using the ultrabright fluorescent nanosphere-based test strips with more convenience and higher efficiency (detection time <30 min). Results demonstrated that the fluorescence intensity of the test line exhibited a good linear relationship respectively with the PD-L1 levels of tumor cell- (R2 = 0.993) and immune cell-derived EVs (R2 = 0.982) in human saliva. By assessing the levels of PD-L1+ EV subpopulations, our test strips hold immense potential for advancing the application of PD-L1+ EV subpopulation-based predictions in tumor diagnosis and prognosis evaluation. In summary, by integrating the benefits of FNs and lateral flow chromatography, we here provide a strategy to accurately measure the cargo levels of EVs originating from diverse cell sources in bodily fluids.

Over the past decades, nanomedicine researchers have dedicated their efforts to developing nanoscale platforms capable of more precisely delivering drug payloads to attack tumors. Cancer nanovaccines are exhibiting a distinctive capability in inducing tumor-specific antitumor responses. Nevertheless, there remain numerous challenges that must be addressed for cancer nanovaccines to evoke sufficient therapeutic effects. Cell membrane-derived nanovaccines are an emerging class of cancer vaccines that comprise a synthetic nanoscale core camouflaged by naturally derived cell membranes. The specific cell membrane has a biomimetic nanoformulation with several distinctive abilities, such as immune evasion, enhanced biocompatibility, and tumor targeting, typically associated with a source cell. Here, we discuss the advancements of cell membrane-derived nanovaccines and how these vaccines are used for cancer therapeutics. Translational endeavors are currently in progress, and additional research is also necessary to effectively address crucial areas of demand, thereby facilitating the future successful translation of these emerging vaccine platforms.

Extracellular vesicles (EVs) are membrane-bound nanoparticles for intercellular communication. Subtypes of EVs, namely exosomes and microvesicles transfer diverse, bioactive cargo to their target cells and eventually interfere with immune responses. Despite being a promising approach, cancer immunotherapy currently faces several challenges including immune resistance. EVs secreted from various sources in the tumor microenvironment provoke immune cell exhaustion and lower the efficacy of immunological treatments, such as CAR T cells and immune checkpoint inhibitors.

This article goes through the mechanisms of action of various types of EVs in inhibiting immune response and immunotherapies, and provides a comprehensive review of EV-based treatments.

By making use of the distinctive features of EVs, natural or modified EVs are innovatively utilized as novel cancer therapeutics. They are occasionally coupled with currently established treatments to overcome their inadequacies. Investigating the properties and interactions of EVs and EV-based treatments is crucial for determining future steps in cancer therapeutics.

Drug resistance presents a significant challenge to achieving positive clinical outcomes in anti-tumor therapy. Prior research has illuminated reasons behind drug resistance, including increased drug efflux, alterations in drug targets, and abnormal activation of oncogenic pathways. However, there's a need for deeper investigation into the impact of drug-resistant cells on parental tumor cells and intricate crosstalk between tumor cells and the malignant tumor microenvironment (TME). Recent studies on extracellular vesicles (EVs) have provided valuable insights. EVs are membrane-bound particles secreted by all cells, mediating cell-to-cell communication. They contain functional cargoes like DNA, RNA, lipids, proteins, and metabolites from mother cells, delivered to other cells. Notably, EVs are increasingly recognized as regulators in the resistance to anti-cancer drugs. This review aims to summarize the mechanisms of EV-mediated anti-tumor drug resistance, covering therapeutic approaches like chemotherapy, targeted therapy, immunotherapy and even radiotherapy. Detecting EV-based biomarkers to predict drug resistance assists in bypassing anti-tumor drug resistance. Additionally, targeted inhibition of EV biogenesis and secretion emerges as a promising approach to counter drug resistance. We highlight the importance of conducting in-depth mechanistic research on EVs, their cargoes, and functional approaches specifically focusing on EV subpopulations. These efforts will significantly advance the development of strategies to overcome drug resistance in anti-tumor therapy.

Adoptive cellular therapy is a promising strategy for cancer treatment. However, the effectiveness of this therapy is limited by its intricate and immunosuppressive tumor microenvironment. In this study, a targeted therapeutic strategy for macrophage loading of drugs is presented to enhance anti-tumor efficacy of macrophages. K7M2-target peptide (KTP) is used to modify macrophages to enhance their affinity for tumors. Pexidartinib-loaded ZIF-8 nanoparticles (P@ZIF-8) are loaded into macrophages to synergistically alleviate the immunosuppressive tumor microenvironment synergistically. Thus, the M1 macrophages decorated with KTP carried P@ZIF-8 and are named P@ZIF/M1-KTP. The tumor volumes in the P@ZIF/M1-KTP group are significantly smaller than those in the other groups, indicating that P@ZIF/M1-KTP exhibited enhanced anti-tumor efficacy. Mechanistically, an increased ratio of CD4+ T cells and a decreased ratio of MDSCs in the tumor tissues after treatment with P@ZIF/M1-KTP indicated that it can alleviate the immunosuppressive tumor microenvironment. RNA-seq further confirms the enhanced immune cell function. Consequently, P@ZIF/M1-KTP has great potential as a novel adoptive cellular therapeutic strategy for tumors.

This study investigates the intricate interplay between environmental pollutants and exosomes, shedding light on a novel paradigm in environmental health and disease. Cellular stress, induced by environmental toxicants or disease, significantly impacts the production and composition of exosomes, crucial mediators of intercellular communication. The heat shock response (HSR) and unfolded protein response (UPR) pathways, activated during cellular stress, profoundly influence exosome generation, cargo sorting, and function, shaping intercellular communication and stress responses. Environmental pollutants, particularly lipophilic ones, directly interact with exosome lipid bilayers, potentially affecting membrane stability, release, and cellular uptake. The study reveals that exposure to environmental contaminants induces significant changes in exosomal proteins, miRNAs, and lipids, impacting cellular function and health. Understanding the impact of environmental pollutants on exosomal cargo holds promise for biomarkers of exposure, enabling non-invasive sample collection and real-time insights into ongoing cellular responses. This research explores the potential of exosomal biomarkers for early detection of health effects, assessing treatment efficacy, and population-wide screening. Overcoming challenges requires advanced isolation techniques, standardized protocols, and machine learning for data analysis. Integration with omics technologies enhances comprehensive molecular analysis, offering a holistic understanding of the complex regulatory network influenced by environmental pollutants. The study underscores the capability of exosomes in circulation as promising biomarkers for assessing environmental exposure and systemic health effects, contributing to advancements in environmental health research and disease prevention.

There is no theory to quantitatively describe the complex tumor ecosystem. At the same time, cancer immunotherapy is considered a revolution in oncology, but the methods used to describe tumors and the criteria used to evaluate efficacy are not keeping pace. The purpose of this study is to establish a new theory for quantitatively describing the tumor ecosystem, innovating the methods of tumor characterization, and establishing new efficacy evaluation criteria for cancer immunotherapy.

Based on the mathematization of immune equilibrium theory and the establishment of immunodynamics in a previous study, the method of reverse immunodynamics was used, namely, the immune braking force was regarded as the tumor ecological force and the immune force was regarded as the tumor ecological braking force, and the concept of momentum in physics was applied to the tumor ecosystem to establish a series of tumor ecodynamic equations. These equations were used to solve the fundamental and applied problems of the complex tumor ecosystem.

A series of tumor ecodynamic equations were established. The tumor ecological momentum equations and their component factors could be used to distinguish disease progression, pseudoprogression, and hyperprogression in cancer immunotherapy. On this basis, the adjusted tumor momentum equations were established to achieve the equivalence of tumor activity (including immunosuppressive activity and metabolic activity) and tumor volume, which could be used to calculate individual disease remission rate and establish new efficacy evaluation criteria (ieRECIST) for immunotherapy of solid tumor based on tumor ecodynamics. At the same time, the concept of moving cube-to-force square ratio and its expression were proposed to calculate the area under the curve of tumor ecological braking force of blood required to achieve an individual disease remission rate when the adjusted tumor ecological momentum was known.

A new theory termed tumor ecodynamics emphasizing both tumor activity and tumor volume is established to solve a series of basic and applied problems in the complex tumor ecosystem. It can be predicted that the future will be the era of cancer immune ecotherapy that targets the entire tumor ecosystem.

Cancer remains one of the main causes of death in the world due to its increasing incidence and treatment difficulties. Although significant progress has been made in this field, innovative approaches are needed to reduce tumor incidence, progression, and spread. In particular, the development of cancer vaccines is currently ongoing as both a preventive and therapeutic strategy. This concept is not new, but few vaccines have been approved in oncology. Antigen-based vaccination emerges as a promising strategy, leveraging specific tumor antigens to activate the immune system response. However, challenges persist in finding suitable delivery systems and antigen preparation methods. Exosomes (EXs) are highly heterogeneous bilayer vesicles that carry several molecule types in the extracellular space. The peculiarity is that they may be released from different cells and may be able to induce direct or indirect stimulation of the immune system. In particular, EX-based vaccines may cause an anti-tumor immune attack or produce memory cells recognizing cancer antigens and inhibiting disease development. This review delves into EX composition, biogenesis, and immune-modulating properties, exploring their role as a tool for prevention and therapy in solid tumors. Finally, we describe future research directions to optimize vaccine efficacy and realize the full potential of EX-based cancer immunotherapy.

Tumor-mediated immunosuppression is a fundamental obstacle to the development of dendritic cell (DC)-based cancer vaccines, which despite their ability to stimulate host anti-tumor CD8 T cell immunity, have not been able to generate meaningful therapeutic responses. Exosomes are inactive membrane vesicles that are nanoscale in size and are produced by the endocytic pathway. They are essential for intercellular communication. Additionally, DC-derived exosomes (DEXs) contained MHC class I/II (MHCI/II), which is frequently complexed with antigens and co-stimulatory molecules and is therefore able to prime CD4 and CD8 T cells that are specific to particular antigens. Indeed, vaccines with DEXs have been shown to exhibit better anti-tumor efficacy in eradicating tumors compared to DC vaccines in pre-clinical models of digestive system tumors. Also, there is room for improvement in the tumor antigenic peptide (TAA) selection process. DCs release highly targeted exosomes when the right antigenic peptide is chosen, which could aid in the creation of DEX-based antitumor vaccines that elicit more targeted immune responses. Coupled with their resistance to tumor immunosuppression, DEXs-based cancer vaccines have been heralded as the superior alternative cell-free therapeutic vaccines over DC vaccines to treat digestive system tumors. In this review, current studies of DEXs cancer vaccines as well as potential future directions will be deliberated.

Cancer-associated fibroblasts (CAFs), a class of stromal cells in the tumor microenvironment (TME), play a key role in controlling cancer cell invasion and metastasis, immune evasion, angiogenesis, and resistance to chemotherapy. CAFs mediate their activities by secreting soluble chemicals, releasing exosomes, and altering the extracellular matrix (ECM). Exosomes contain various biomolecules, such as nucleic acids, lipids, and proteins. microRNA (miRNA), a 22-26 nucleotide non-coding RNA, can regulate the cellular transcription processes. Studies have shown that miRNA-loaded exosomes secreted by CAFs engage in various regulatory communication networks with other TME constituents. This study focused on the roles of CAF-derived exosomal miRNAs in generating cancer malignant characteristics, including immune modulation, tumor growth, migration and invasion, epithelial-mesenchymal transition (EMT), and treatment resistance. This study thoroughly examines miRNA's dual regulatory roles in promoting and suppressing cancer. Thus, changes in the CAF-derived exosomal miRNAs can be used as biomarkers for the diagnosis and prognosis of patients, and their specificity can be used to develop newer therapies. This review also discusses the pressing problems that require immediate attention, aiming to inspire researchers to explore more novel avenues in this field.

Through their ability to modify the tumor microenvironment and cancer cells, macrophages play a crucial role in the promotion of tumorigenesis, development of tumors and metastasis, and chemotherapy resistance. A growing body of research has indicated that exosomes may be essential for coordinating the communication between cancer cells and macrophages. One type of extracellular vehicle called an exosome is utilized for delivering a variety of molecules, such as proteins, lipids, and nucleic acids, to specific cells in order to produce pleiotropic effects. Exosomes derived from macrophages exhibit heterogeneity across various cancer types and function paradoxically, suppressing tumor growth while stimulating it, primarily through post-transcriptional control and protein phosphorylation regulation in the receiving cells. Exosomes released by various macrophage phenotypes offer a variety of therapeutic alternatives in the interim. We outlined the most recent developments in this article, including our understanding of the roles that mechanisms and macrophage-derived exosomal biogenesis play in mediating the progression of cancer and their possible therapeutic uses.