Parasites generally survive in their hosts by employing various immunomodulation and immune evasion mechanisms. "helminth therapy" is one strategy that harnesses these parasite-specific beneficial properties for the therapeutic treatment of autoimmune and allergic diseases. Although numerous experimental reports have documented the anti-autoimmune activities of parasitic infections and parasite-derived products, the underlying mechanisms remain insufficiently elucidated due to the significant diversity among parasite species and autoimmune conditions. Rheumatoid arthritis (RA) is one of the most prevalent autoimmune disorders, presenting a substantial opportunity for the therapeutic use of parasites as novel disease-modifying antirheumatic drugs (DMARDs). In this paper, we summarize the immunomodulatory properties of parasites, focusing on their anti-arthritic mechanisms, and discuss the potential of parasite-derived products for the treatment of RA.

Oral cancer, a prevalent form of head and neck malignancy, accounts for 4% of global cancer cases. The most common type, oral squamous cell carcinoma (OSCC), has a survival rate of about 50%. Even though emerging molecular therapies show promise for managing oral cancer, current treatments like surgery, radiotherapy, and chemotherapy have significant side effects. In addition, the complex tumor microenvironment (TME), involving the extracellular matrix (ECM) and cells like fibroblasts and stromal cells like immune cells, promotes tumor growth and inhibits immune responses, complicating treatment. Nonetheless, immunotherapy is crucial in cancer treatment, especially in oral cancers. Indeed, its effectiveness lies in targeting immune checkpoints such as PD-1 and CTLA-4 inhibitors, as well as monoclonal antibodies like pembrolizumab and cetuximab, adoptive cell transfer methods (including CAR-T cell therapy), cytokine therapy such as IL-2, and tumor vaccines. Thus, these interventions collectively regulate tumor proliferation and metastasis by targeting the TME through autocrine-paracrine signaling pathways. Immunotherapy indeed aims to stimulate the immune system, leveraging both innate and adaptive immunity to counteract cancer cell signals and promote tumor destruction. This review will explore how the TME controls tumor proliferation and metastasis via autocrine-paracrine signaling pathways. It will then detail the effectiveness of immunotherapy in oral cancers, focusing on immune checkpoints, targeted monoclonal antibodies, adoptive cell transfer, cytokine therapy, and tumor vaccines.

Stomach adenocarcinoma (STAD) with microsatellite instability (MSI) is associated with a better prognosis compared to Non-MSI. This study aims to elucidate the differences in the tumor microenvironment (TME) of MSI and explore its underlying mechanisms in STAD.

TME differences between MSI and Non-MSI were analyzed using single-cell RNA sequencing (MSI = 7, Non-MSI = 19) and bulk RNA sequencing (MSI = 39, Non-MSI = 198). Differentially expressed genes (DEGs) were used to identify enriched pathways and hub genes. TNFSF9 expression was validated by immunohistochemistry (IHC) on 23 STAD sections (MSI = 13, Non-MSI = 10) and confirmed in tumor epithelial cells using SNU-1 (MSI) and AGS (Non-MSI) cell lines through quantitative polymerase chain reaction (qPCR) and Western blot (WB).

The results showed MSI was significantly associated with a better prognosis (P < 0.05). Within the TME, MSI was associated with a higher abundance of antigen-presenting cells, including M1 macrophages (40.1% vs. 27.9%) and activated dendritic cells (22.1% vs. 10.5%), as well as pro-inflammatory Th1-like CD4⁺ T cells (15% vs. 11%). However, MSI also showed an increase in exhausted T cells, indicating a complex immune landscape. Signaling pathway and cell communication analyses revealed an enrichment of cytokine-related pathways in MSI. Hub gene analysis revealed that TNFSF9 was predominantly expressed in stromal cells and partially in tumor epithelial cells in MSI, with its upregulation further confirmed through IHC, qPCR, and WB. Correlation analysis demonstrated a positive relationship between TNFSF9 expression and the abundance of M1 macrophages.

These findings provide new insights into the TME of MSI in STAD, emphasizing the significant role of TNFSF9 in shaping MSI-specific TME, enhancing immunotherapy efficacy, and improving patient survival.

BackgroundRecent findings indicate a correlation between the peripheral adaptive immune system and neuroinflammation in Alzheimer's disease (AD).ObjectiveTo characterize the composition of adaptive immune cells in the peripheral blood of AD patients.MethodsWe utilized single-cell mass cytometry (CyTOF) to profile peripheral blood mononuclear cells (PBMCs). Concurrently, we assessed the concentration of proteins associated with AD and neuroinflammation in the plasma of the same subjects.ResultsWe found that the abundance of proinflammatory CXCR3 + CD127+ Type 1 T helper (Th1) cells in AD patients was negatively correlated with the abundance of neurofilament light chain protein. This correlation is apolipoprotein E (ApoE) ε4-dependent. Analyzing public single-cell RNA-sequencing (scRNA-seq) data, we found that, contrary to the scenario in the peripheral blood, the cell frequency of CXCR3 + CD127+ Th1 cells in the cerebrospinal fluid (CSF) of AD patients was increased compared to healthy controls (HCs). Moreover, the proinflammatory capacity of CXCR3+ CD127+ Th1 cells in the CSF of AD patients was further increased compared to HCs.ConclusionsThese results reveal an association of a peripheral T-cell change with neuroinflammation in AD and suggest that dysregulation of peripheral adaptive immune responses, particularly involving CXCR3 + CD127+ Th1 cells, may potentially be mediated by factors such as ApoE ε4 genotype.

COVID-19, caused by SARS-CoV-2, has become a global public health threat. Although no replication-competent virus has been found in breast milk samples, breastfeeding practices during the pandemic were impacted. It is well known that breast milk is adapted to meet the needs of infants, providing the appropriate amounts of nutrients and various bioactive compounds that contribute to the maturation of the immune system and antioxidant protection, safeguarding infants against diseases. While its composition is variable, breast milk contains immune cells, antibodies, and cytokines, which have anti-inflammatory, pro-inflammatory, antiviral, and antibacterial properties that strengthen infant immunity. Since COVID-19 vaccines have not yet been approved for infants under six months of age, newborns rely on the passive transfer of antibodies via the placenta and breast milk to protect them against severe SARS-CoV-2 infection. Several studies that analyzed breast milk samples in the context of COVID-19 have demonstrated that a strong antibody response is induced following maternal infection with SARS-CoV-2. Therefore, this review aims to provide a comprehensive overview of the impact of maternal exposure to SARS-CoV-2 through natural infection and/or vaccination on the immunological composition of breast milk based on the studies conducted on this topic.

Cyclophosphamide is a widely used chemotherapeutic agent known for its effectiveness in treating various cancers; however, it is associated with significant immunosuppressive side effects. This study investigates the potential of sakuranetin, a natural flavonoid, in mice under cyclophosphamide-induced immunosuppressive conditions. Mice were grouped into four groups: one control group, two treated with cyclophosphamide and two sakuranetin-treated groups receiving different doses (10 and 20 mg/kg). Immune organ indices, lymphocyte proliferation, hematological parameters, nitric oxide levels, cytokines (tumor necrosis factor alpha-TNF-α, interferon γ-IFN-γ), interleukins (interleukin-1β-IL-1β, IL-4, IL-6), immunoglobulin G (IgG), IgM levels, plague-forming cells quantification, qualitative hemolysis, and delayed-type hypersensitivity were assessed. Cyclophosphamide significantly (P < 0.05) reduced immune organ indices, lymphocyte proliferation, changes in hematological parameters, and nitric oxide levels. Treatment with both sakuranetin doses restored these parameters and normalized cytokine, IgG, and IgM levels (P < 0.05). Sakuranetin significantly (P < 0.05) improved the immunomodulatory action with elevated immune response with downregulation in immune response mediated by cells. Sakuranetin effectively counteracts cyclophosphamide-induced immunosuppression by modulating the IFN-γ, TNF-α, IgG, and interleukin pathway, suggesting its potential as a protective agent.

Atopic dermatitis (AD), a chronic inflammatory skin disease whose incidence is increasing worldwide, requires the development of alternative treatments due to limited treatment options and concerns about side effects of therapeutic agents. Aspalathin (ASP) is the primary flavonoid found in rooibos, an herb traditionally used for allergies and eczema, accounting for over 40 % of the total flavonoid content, especially in its unfermented state (Green rooibos). This research conducted a thorough investigation into the pharmacological properties of ASP on AD, emphasizing local responses via activated keratinocytes, systemic responses involving T cells and basophils, and an integrated assessment using an AD mouse model. Topical application of ASP significantly reduced AD phenotypes, including erythema, scaling, and increased skin thickness, in AD mouse model. Histological analysis indicated a decrease in the infiltration of immune cells in skin lesions. Moreover, ASP down-regulated inflammatory markers, including T helper (Th)1 and Th2 cytokines, in both skin tissues and activated mouse T cells. In particular, ASP significantly reduced serum immunoglobulin (Ig)E and IgG2a levels. ASP suppressed the expression of cytokines linked to allergy and inflammation in T cells, basophils, and keratinocytes. Mechanistically, ASP exhibited anti-inflammatory properties by inhibiting STAT6 and NFAT1 activation in AD mouse skin and in activated T cells, basophils, and keratinocytes. In conclusion, ASP displayed pronounced effectiveness in relieving AD by sophisticated modulation of immune responses across both local and systemic domains. These findings highlight ASP's promise as a therapeutic intervention for AD, providing a solid scientific basis for future exploration and development.

Breast cancer is the most common type of cancer in women and the second leading cause of death by cancer. Despite recent advances, the mortality rate remains high, underlining the need to develop new therapeutic approaches. The complex interaction between cancer cells and the tumor microenvironment (TME) is crucial in determining tumor progression, therapy response, and patient prognosis. Understanding the role of immune cells in carcinogenesis and tumor progression can help improve targeted therapeutic options, increasing the likelihood of a favorable prognosis. Therefore, this review aims to critically analyze the complex interaction between tumor cells and immune cells, emphasizing the clinical and therapeutic implications. Additionally, we explore advances in immunotherapies, with a focus on immune checkpoint inhibitors.

In critical illness, all elements of gut function are perturbed. Dysbiosis develops as the gut microbial community loses taxonomic diversity and new virulence factors appear. Intestinal permeability increases, allowing for translocation of bacteria and/or bacterial products. Epithelial function is altered at a cellular level and homeostasis of the epithelial monolayer is compromised by increased intestinal epithelial cell death and decreased proliferation. Gut immunity is impaired with simultaneous activation of maladaptive pro- and anti-inflammatory signals leading to both tissue damage and susceptibility to infections. Additionally, splanchnic vasoconstriction leads to decreased blood flow with local ischemic changes. Together, these interrelated elements of gastrointestinal dysfunction drive and then perpetuate multi-organ dysfunction syndrome. Despite the clear importance of maintaining gut homeostasis, there are very few reliable measures of gut function in critical illness. Further, while multiple therapeutic strategies have been proposed, most have not been shown to conclusively demonstrate benefit, and care is still largely supportive. The key role of the gut in critical illness was the subject of the tenth Perioperative Quality Initiative meeting, a conference to summarize the current state of the literature and identify key knowledge gaps for future study. This review is the product of that conference.

Infertility, impacting a significant number of couples, is characterized by the failure to conceive after one year of consistent, unprotected sexual intercourse. It is multifactorial, with etiological contributors including ovulatory dysfunction, male reproductive anomalies, and tubal patency issues. Approximately 15% of infertility cases are classified as "unexplained," highlighting the complexity of this condition. Lifestyle determinants such as obesity and smoking further complicate reproductive outcomes, while infertility can also indicate underlying chronic health conditions. A specialized category, immune infertility, arises from a breakdown of immunological tolerance, an essential aspect for conception and the maintenance of pregnancy. The role of various immunological components, including immune cells, cytokines, chemokines, factors like HLA-G, etc., is pivotal in this context. Moreover, non-coding RNAs (ncRNAs) have emerged as critical regulators of immune tolerance within the reproductive axis. This review synthesizes the complex immunological pathways vital for successful implantation and the early stages of pregnancy alongside the regulatory roles of ncRNAs in these processes. Offering an integrated view of molecular and immunological interactions associated with infertility seeks to enhance our understanding of potential strategies to facilitate successful conception and sustain early pregnancy.

Tyrosine kinase inhibitors (TKIs) have transformed the treatment of epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer. However, treatment resistance remains a major challenge in clinical practice. The tumor microenvironment (TME) is a complex system composed of tumor cells, immune and non-immune cells, and non-cellular components. Evidence indicates that dynamic changes in TME during TKI treatment are associated with the development of resistance. Research has focused on identifying how each component of the TME interacts with tumors and TKIs to understand therapeutic targets that could address TKI resistance. In this review, we describe how TME components, such as immune cells, fibroblasts, blood vessels, immune checkpoint proteins, and cytokines, interact with EGFR-mutant tumors and how they can promote resistance to TKIs. Furthermore, we discuss potential strategies targeting TME as a novel therapeutic approach.

Staphylococcus aureus (S. aureus) is a Gram-positive bacterium of significant clinical importance, known for its versatility and ability to cause a wide array of infections, such as osteoarticular, pulmonary, cardiovascular, device-related, and hospital-acquired infections. This review describes the most recent evidence of the pathogenic potential of S. aureus, which is commonly part of the human microbiota but can lead to severe infections. The prevalence of pathogenic S. aureus in hospital and community settings contributes to substantial morbidity and mortality, particularly in individuals with compromised immune systems. The immunopathogenesis of S. aureus infections involves intricate interactions with the host immune and non-immune cells, characterized by various virulence factors that facilitate adherence, invasion, and evasion of the host's defenses. This review highlights the complexity of S. aureus infections, ranging from mild to life-threatening conditions, and underscores the growing public health concern posed by multidrug-resistant strains, including methicillin-resistant S. aureus (MRSA). This article aims to provide an updated perspective on S. aureus-related infections, highlighting the main diseases linked to this pathogen, how the different cell types, virulence factors, and signaling molecules are involved in the immunopathogenesis, and the future perspectives to overcome the current challenges to treat the affected individuals.

Diabetic ulcer is a serious diabetes complication and a primary reason for amputations. For many years, the San Huang Xiao Yan (SHXY) recipe has served as a conventional remedy for these ulcers, effectively reducing inflammatory factors and exhibiting considerable therapeutic efficacy. However, the precise mechanism remains incompletely understood.

To explore the efficacy and mechanisms of SHXY and its active ingredients in treating diabetic ulcer.

A diabetic ulcer mouse model was established using C57BL/6J mice on a high-fat diet, followed by streptozotocin injection and skin damage. We investigated the bioactive compounds, key targets, and pharmacological mechanisms of SHXY in addressing diabetic ulcers through network pharmacology, molecular docking, both in vitro and in vivo validation experiments.

One week after intragastric administration, SHXY can reduce inflammation and edema, increase collagen synthesis, and reduce the expression of RORγT and IL-17A without affecting Treg cells. In vitro, SHXY-containing serum inhibited the differentiation of Th17 cells but did not affect Treg and Th1 cells. Network pharmacology found that SHXY acts through inflammatory pathways, including TNF, IL-17, Th17 cell differentiation, HIF-1, and PI3K-Akt.

SHXY and its candidate enhance healing in diabetic ulcers by modulating CD4+ T cells, particularly by inhibiting Th17 cell differentiation.

Immunotherapy can be a sensible alternative because invasive Staphylococcus aureus infection mortality, morbidity, and cost are still alarmingly high despite the development of multiple new medications to treat methicillin-resistant S. aureus infections. Herein, killed whole-cell Staphylococcus aureus was formulated in Montanide ISA266 and Alum adjuvants, and the potency and efficacy of the vaccine were studied. After the preparation of two kinds of whole-cell vaccine (bacterin and lysate), 20 µg of each vaccine candidate was formulated in Montanide ISA266 and Alum adjuvants, then subcutaneously injected in distinct groups. Blood samples were taken two weeks after each booster injection, and two booster shots were given at 2-week intervals. Sera were examined by ELISA for total IgG, isotypes (IgG1 and IgG2a), and cytokine production (IFN-γ and IL-4), respectively, to ascertain the kind of induced immune response. Experimental mice were challenged intraperitoneally with 5 × 108 CFU of bacteria 2 weeks after their last immunization, and the mortality rate and bacterial load were measured. Both immunogens elicited strong humoral immune responses, producing antibodies that improved opsonic capability, IFN-γ, and IL-4 production and protectivity in response to the experimental challenge. Compared to other immunized groups, the lysate formulation with Montanide ISA266 produced a greater antibody titer and IgG1 isotype and showed the highest vaccine potency. Additionally, combining the whole-cell vaccine (bacterin and lysate) with the adjuvant Montanide ISA266 increased IFN-γ and IL-4 cytokines response and protection in the experimental challenge. These findings show that avoiding S. aureus infection using active vaccination with inactivated whole-cell vaccines (bacterin and lysate) may be a successful strategy. The type of adjuvant in the vaccine formulation is important and influences vaccine potency and efficacy.

Myasthenia gravis (MG) presents with symptoms that significantly affect patients' daily lives. Long-term MG therapies may lead to substantial side effects, predominantly due to prolonged immune suppression. Sirt6, which plays a vital role in maintaining cellular homeostasis and is recognised for its involvement in cytokine production in immune cells, has not yet been explored in relation to MG. PBMCs and CD4+ T cells were isolated from blood samples. RT-qPCR, western blot and ELISA were used to assess the expression of target genes and proteins. Flow cytometry was used to identify the subsets of T helper cells. Co-IP was conducted to investigate the interaction between USP9X and Sirt6. Finally, the experimental autoimmune myasthenia gravis (EAMG) model was established. In MG patients, Sirt6 levels were downregulated compared to healthy controls. Sirt6 overexpression led to a reduction in Th1 and Th17 cell populations while augmenting Treg cells in PBMCs. USP9X interacted with Sirt6, leading to its deubiquitination and stabilisation. Elevated Sirt6 levels subsequently mitigated symptoms in the EAMG model. The stabilisation of Sirt6, mediated by USP9X, has been found to relieve symptoms of EAMG by influencing the subtypes of T helper cells. This highlights the promising potential of Sirt6 as a viable therapeutic target in the treatment of MG.

T helper (Th) and regulatory T (Treg) cells regulate atherosclerosis, plaque, inflammation to involve in acute coronary syndrome (ACS). The current study aimed to investigate the clinical implications of Th and Treg cells in ACS patients receiving percutaneous coronary intervention (PCI). Blood Th1, Th2, Th17 and Treg cells were detected in 160 ACS patients before PCI, after PCI, at 1 month (M). Short physical performance battery (SPPB) at M1/M3 and major adverse cardiac event (MACE) during follow-ups were evaluated. Th1 and Th17 both showed upward trends during PCI, then greatly declined at M1 (P < 0.001). Th2 exhibited an upward trend during PCI but decreased slightly at M1 (P < 0.001). Treg remained stable during PCI but elevated at M1 (P < 0.001). Moreover, a positive correlation between Th1 and Th17, a negative correlation between Th17 and Treg, were discovered at several timepoints (most P < 0.050). Interestingly, the receiver operating curve (ROC) analyses revealed that Th1 [area under curve (AUC) between 0.633-0.645] and Th17 (AUC between 0.626-0.699) exhibited values estimating SPPB score <= 6 points at M1 or M3 to some extent. Importantly, Th1 (AUC between 0.708-0.710), Th17 (AUC between 0.694-0.783), and Treg (AUC between 0.706-0.729) predicted MACE risk. Multivariate models involving Th and Treg cells along with other characteristics revealed acceptable values estimating SPPB score <= 6 points at M1 or M3 (AUC between 0.690-0.813), and good values predicting MACE risk (AUC between 0.830-0.971). Dynamic variations in Th and Treg cells can predict the prognosis of ACS patients receiving PCI.

The pivotal role of antibody-producing B cells in controlling hepatitis B virus (HBV) infection is well-established. However, the antiviral role of B cells extends beyond antibody production, which has been insufficiently studied for HBV infection.

Using an HBV hydrodynamic injection (HDI) mouse model with B cell depletion or functional blockade, we detected HBV infection markers and assessed T cell function through enzyme-linked immunosorbent assay, RT-PCR and flow cytometry.

We observed significantly delayed serum and intrahepatic HBV clearance in permanently B cell-deficient and transiently B cell-depleted mice as well as mice with a functional B cell blockade. Blocking B cell function prior to or soon after HBV HDI resulted in delayed HBV clearance indicating that B cells contribute to initiating anti-HBV immune responses after following HBV exposure. Additionally, we also found an early activation of B cells following HBV exposure, characterized by an upregulation of MHC-II, CXCR5, and PD-1. Critically, the proliferation and activation of both CD4 + and CD8 + T cells were impaired after B cell depletion prior to HBV challenge. Consistently, depleting B cells reduced the generation of Th1, Th2, and Th17 cells in the spleen and hindered HBV-specific CD8 + T cell responses in the liver. Along these lines, the HBV-exposed B cells were more efficient in inducing HBcAg-specific CD8 + T cell responses in vitro.

Collectively, our data indicate that B cells, in addition to antibody production, are essential for the development of anti-HBV cellular responses and intrahepatic HBV clearance during the early stage of HBV antigen exposure.

Immunotherapy has made progress in the treatment of tumours; however, in patients with pancreatic cancer, immunotherapy has not achieved effective results. The present study investigated changes in the immune microenvironment during tumour development and progression, and the relationship between the immune microenvironment and prognosis, to clarify the mechanism of immune escape in pancreatic cancer. A total of 40 patients with pancreatic cancer (including 22 with stage I-II disease and 18 with stage III-IV disease) and 20 patients with chronic pancreatitis were included in the present study. The expression of CD3, CD4, CD8, CD56, IFN-γ, IL-17 and 4-1BBL was assessed by immunohistochemistry, and the mRNA expression levels were detected by reverse transcription-quantitative PCR (RT-qPCR). The clinicopathological characteristics and prognoses of patients with pancreatic cancer were analysed to further explore the role of IL-17, IFN-γ, 4-1BBL and tumour-infiltrating lymphocytes in pancreatic cancer. Notably, the expression levels of CD3, CD8, CD56, IFN-γ and 4-1BBL in patients with stages I-II and III-IV cancer were lower than those in patients with chronic pancreatitis (P<0.05), especially in patients with stage III-IV cancer (P<0.05). In addition, the expression of IL-17 in patients with stages I-II and III-IV cancer was greater than in patients with chronic pancreatitis (P<0.05), especially in patients with stage III-IV cancer (P<0.05). The RT-qPCR results regarding CD3, CD4, CD8, CD56, IFN-γ and IL-17 were almost the same as those obtained from immunohistochemical analysis; however, the mRNA expression levels of 4-1BBL were not significantly different between stages I-II and III-IV. Furthermore, patients with pancreatic cancer with higher expression levels of CD3, CD8, CD56, IFN-γ and 4-1BBL exhibited longer survival, whereas those with higher expression of IL-17 had a shorter survival time. The expression levels of CD3, CD8, CD56, cytokines IL-17 and IFN-γ, and costimulatory molecule 4-1BBL were revealed to be related to the degree of differentiation, Tumour-Node-Metastasis staging and the prognosis of pancreatic cancer, and may serve as novel immunological indicators for evaluating the condition and treatment effectiveness in patients with pancreatic cancer.

Eczema is the most common category of inflammatory skin disorders as dermatologists see many patients with eczematous diseases in daily practice. It is characterized by the three major morphological features: multiple-pinpoint condition, polymorphism, and itch. To describe polymorphism, "eczema triangle" has been used in German/Japanese dermatology. The multiple pinpoints correspond to numerous tiny foci from which individual papules/vesicles arise. The polymorphism betrays composition of erythema, papule, seropapule, vesicle, pustule, scale, and crust, which are seen in acute eczema. Meanwhile, chronic eczema is represented by lichenification and hyperpigmentation, and possibly by hypopigmentation. In acute eczema, spongiosis is associated with overproduction of hyaluronic acid, secretion of self-protective galectin-7, and decreased expression of E-cadherin. In the upper dermis, Th1/Tc1 or Th2/Tc2, and additional Th17, Th22, and/or Tc22 infiltrate, depending on each eczematous disease. Innate lymphoid cells are also involved in the formation of eczema. In chronic eczema, periostin contributes to remodeling of inflammatory skin with dermal fibrosis, and epidermal melanogenesis and dermal pigment deposition result in hyperpigmentation. Finally, eczematous diseases are potentially associated with increased risk of comorbidities, including not only other allergic diseases but also coronary heart disease and mental problems such as depression. Although the original word for eczema is derived from old Greek "ekzein," eczema remains a major target of modern science and novel therapies.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by recurrent eczematous lesions and severe itching, for which clinical treatments are limited. Selectively inhibiting Janus Kinase 3 (JAK3) and tyrosine kinase expressed in hepatocellular carcinoma (TEC) family kinases is proposed as a promising strategy to treat AD with possible reduced side effects and enhanced efficacy. In this study, we developed a dual JAK3/TEC family kinase inhibitor ZZB, which demonstrated potent inhibitory activity with IC50 values of 0.89 nM against JAK3 and 11.56 nM against TEC kinase interleukin-2-inducible T-cell kinase (ITK). Docking studies revealed that ZZB forms a covalent bond with the unique cysteine residue at position 909 (Cys909) in JAK3 and Cys442 in ITK. Utilizing human peripheral blood mononuclear cells, we discovered ZZB selectively inhibits JAK3-dependent cytokines signaling and ITK-mediated CD4+ T cell activation. Moreover, in vitro studies indicated ZZB significantly suppresses the proliferation and differentiation of CD4+ T cells, as well as the cytolytic function of CD8+ T cells and NK cells. We then conducted a pharmacokinetic study in mice and observed a favorable pharmacokinetic profile for ZZB. In a mouse model of AD induced by repeated application of 2,4-dinitrochlorobenzene to the shaved dorsal skin, oral administration of ZZB (100 mg/kg) markedly improved skin condition and reduced immune cell infiltration, matching the efficacy of the positive drug dexamethasone. We conclude that the JAK3/TEC kinase inhibitor ZZB is a highly promising candidate for the treatment of AD.

It is not clear how CD4+ memory T cells are formed from a much larger pool of earlier effector cells. We found that transient systemic bacterial infection rapidly generates several antigen-specific T helper (Th)1 and T follicular helper (Tfh) cell populations with different tissue residence behaviors. Although most cells of all varieties had transcriptomes indicative of cell stress and death at the peak of the response, some had already acquired a memory cell signature characterized by expression of genes involved in cell survival. Each Th1 and Tfh cell type was maintained long term by interleukin (IL)-7, except germinal center Tfh cells, which depended on a T cell antigen receptor (TCR) signal. The results indicate that acute infection induces rapid differentiation of Th1 and Tfh cells, a minority of which quickly adopt the gene expression profile of memory cells and survive by signals from the IL-7 receptor or TCR.

To evaluate and quantitatively describe age-dependent homeostasis for a broad range of total T-cells and specific T-lymphocyte subpopulations in healthy human subjects.

A systematic literature review was performed to identify and collect relevant quantitative information on T-lymphocyte counts in human blood and various organs. Both individual subject and grouped (aggregated) data on T-lymphocyte observations in absolute and relative values were digitized and curated; cell phenotypes, gating strategies for flow cytometry analyses, organs from which observations were obtained, subjects' number and age were also systematically inventoried. Age-dependent homeostasis of each T-lymphocyte subpopulation was evaluated via a weighted average calculation within pre-specified age intervals, using a piece-wise equal-effect meta-analysis methodology.

In total, 124 studies comprising 11722 unique observations from healthy subjects encompassing 20 different T-lymphocyte subpopulations - total CD45+ and CD3+ lymphocytes, as well as specific CD4+ and CD8+ naïve, recent thymic emigrants, activated, effector and various subpopulations of memory T-lymphocytes (total-memory, central-memory, effector-memory, resident-memory) - were systematically collected and included in the final database for a comprehensive analysis. Blood counts of most T-lymphocyte subpopulations demonstrate a decline with age, with a pronounced decrease within the first 10 years of life. Conversely, memory T-lymphocytes display a tendency to increase in older age groups, particularly after ~50 years of age. Notably, an increase in T-lymphocyte numbers is observed in neonates and infants (0 - 1 year of age) towards less differentiated T-lymphocyte subpopulations, while an increase into more differentiated subpopulations emerges later (1 - 5 years of age).

A comprehensive systematic review and meta-analysis of T-lymphocyte age-dependent homeostasis in healthy humans was performed, to evaluate immune T-cell profiles as a function of age and to characterize generalized estimates of T-lymphocyte counts across age groups. Our study introduces a quantitative description of the fundamental parameters characterizing the maintenance and evolution of T-cell subsets with age, based on a comprehensive integration of available organ-specific and systems-level flow cytometry datasets. Overall, it provides the most up-to-date view of physiological T-cell dynamics and its variance and may be used as a consistent reference for gaining further mechanistic understanding of the human immune status in health and disease.

Background: Cold-dampness diarrhea (CDD) is a common gastrointestinal disorder in children, characterized by diarrhea and intestinal barrier dysfunction. Weiling decoction (WLD) is frequently used in clinical practice to treat CDD, a condition triggered by multiple factors. However, the molecular mechanisms underlying its therapeutic effects remain poorly understood. Objectives: This study aimed to evaluate the efficacy of WLD in treating CDD and to elucidate its potential mechanisms. Methods: UPLC-HRMS/MS was employed to identify the chemical constituents of WLD and the absorption components in the plasma of WLD-treated rats. Additionally, a rat model of CDD was established to assess the therapeutic effects of WLD through a comprehensive approach. To elucidate the molecular mechanisms underlying these effects, network pharmacology and transcriptomic analyses were performed to identify potential signaling pathways associated with CDD alleviation. Molecular docking and flow cytometry assays were subsequently utilized to validate the identified signaling pathways. Results: A total of 223 chemical components were detected in WLD, and 49 absorption components were identified in the plasma of WLD-treated rats by UPLC-HRMS/MS. WLD treatment significantly alleviated the symptoms of CDD, reduced intestinal damage, and diminished the inflammatory response. Additionally, WLD influenced key genes in immune-related pathways. Molecular docking revealed strong binding affinities between the main components of WLD and key targets within these pathways. Flow cytometry, along with the analysis of inflammatory cytokines and transcription factors, demonstrated that WLD modulated the balance between Th1/Th2 and Th17/Treg cell populations. Conclusions: This study provides the first evidence that WLD alleviates CDD by regulating the balance between Th1/Th2 and Th17/Treg cell populations. These findings offer a theoretical basis for future investigations into the therapeutic potential of WLD in the treatment of CDD.

Breast cancer is a heterogeneous malignant disease with a varying prognosis and is classified into four molecular subtypes. It remains one of the most prevalent cancers globally, with the tumor microenvironment playing a critical role in disease progression and patient outcomes.

This study evaluated tumor samples from 40 female patients with luminal A and B breast cancer, utilizing flow cytometry to phenotypically characterize the immune cells and tumor cells present within the tumor tissue.

The luminal B-like tumor samples exhibited increased infiltration of CD4+ cells, regulatory T cells (Tregs), and Th17 cells and decreased levels of NK cells, γδ T cells, Th1 cells, and follicular T cells, which is indicative of a more immunosuppressive tumor microenvironment.

These findings suggest that luminal B-like tumors have a microenvironment that is less supportive of effective anti-tumor immune responses compared to luminal A tumors. This study enhances the understanding of the immunological differences between luminal subtypes of breast cancer and identifies potential new therapeutic targets and biomarkers that could drive advancements in precision medicine for breast cancer management.

We aim to explore the immunomodulatory properties of T cells on different titanium nanotubes and the key immunological factors involved in this process.

Transcriptome data from GEO database of healthy people and healthy implants were used to analyze cell infiltration and factor distribution of adaptive immune using bioinformatics tools. T cells from activated rat were cultured on titanium nanotubes that were prepared by anodization with different diameters (P-0, NT15-30 nm, NT40-100 nm, NT70-200 nm). The proliferation and expressions of the main transcription factors and cytokines of T-cells were detected. Magnetic bead sorting of CD3+ T cells and transcriptome sequencing were performed to explore the signaling pathways and key immune factors that may influence the related immune responses.

Bioinformatics analysis showed that healthy peri-implant tissues were enriched by the most of T-cell subtypes. T-cell-mediated adaptive immunological responses involved IL-17A. On the third day, the NT15 and NT40 groups showed significantly higher pro-proliferative effects than the NT70 group (P<0.05). Notably, the NT40 group exhibited the lowest T-bet expression (P<0.05) along with the highest levels of Rorγt, Gata3, and Foxp3(P<0.05), followed by the NT15 group. Additionally, the NT40 group demonstrated reduced RANKL, TNF-α, and IL-6 (P<0.05) and increased OPG and IL-10 (P<0.05). Meanwhile, the NT15 group had lower IFN-γ expression(P>0.05) but higher IL-4, and TGF-β1 expressions(P<0.05). Differential expressed genes (DGEs) of T-cell related to the morphologies of titanium nanotubes were mostly enriched in the IL-17 signaling pathway mediated by IL-17A/F. Gene and protein expressions indicated that the NT40 group had the highest secretion in IL-17A of T cells.

Titanium nanotube morphologies in medium (100 nm) and small (30 nm) sizes significantly influence T cell differentiation and immune factor secretion, with T-cell-derived IL-17A likely playing a key regulatory role.

Autism spectrum disorder (ASD) is a highly heterogeneous disorder characterized by impairments in social, communicative, and restrictive behaviors. Over the past 20 years, research has highlighted the role of the immune system in regulating neurodevelopment and behavior. In ASD, immune abnormalities are frequently observed, such as elevations in pro-inflammatory cytokines, alterations in immune cell frequencies, and dysregulated mechanisms of immune suppression. The adaptive immune system - the branch of the immune system conferring cellular immunity - may be involved in the etiology of ASD. Specifically, dysregulated T cell activity, characterized by altered cellular function and increased cytokine release, presence of inflammatory phenotypes and altered cellular signaling, has been consistently observed in several studies across multiple laboratories and geographic regions. Similarly, mechanisms regulating their activation are also disrupted. T cells at homeostasis coordinate the healthy development of the central nervous system (CNS) during early prenatal and postnatal development, and aid in CNS maintenance into adulthood. Thus, T cell dysregulation may play a role in neurodevelopment and the behavioral and cognitive manifestations observed in ASD. Outside of the CNS, aberrant T cell activity may also be responsible for the increased frequency of immune based conditions in the ASD population, such as allergies, gut inflammation and autoimmunity. In this review, we will discuss the current understanding of T cell biology in ASD and speculate on mechanisms behind their dysregulation. This review also evaluates how aberrant T cell biology affects gastrointestinal issues and behavior in the context of ASD.

Adjuvants are some of the most important components used for vaccine formulation. In addition, the efficacy of vaccines is highly dependent on the nature of the adjuvants used. Therefore, new adjuvant formulations may help develop more potent vaccines. In the present study, the potency of an in-house and water-in-oil adjuvant (Yavar-70A) was compared with Montanide ISA 206 and Montanide ISA 266 in an HPV-16E7d vaccine model.

Three HPV-16 E7d vaccines were formulated using three different adjuvants, Montanide ISA 206, Montanide ISA 266, and Yavar-70A, with standard protocols. Afterward, each formulation containing 10 μg of the E7d protein was administered thrice at two-week intervals to C57BL/6 mice. Serum levels of IFN-γ and IL-4 cytokines secreted from spleen cells, total IgG, and specific IgG1 and IgG2a isotypes were assessed using ELISA two weeks after the last immunization. Lymphocyte proliferative responses were also evaluated using the BrdU method.

The results indicated that the vaccine formulated using the Yavar-70A adjuvant showed the highest lymphocyte proliferation responses compared with other groups and higher IFN-γ cytokine release compared with that formulated using Montanide ISA 206. However, the vaccine formulated using Montanide ISA 206 induced the highest total IgG responses compared with other groups. Importantly, the vaccine formulated using Yavar-70A decreased IL-4 secretion compared with other vaccinated groups.

The present study demonstrated that Yavar-70A induces cellular and humoral immunologic parameters against the HPV-16 E7d vaccine model comparable to commercialized oil-based adjuvants.

Schizothoracine fishes in saltwater lakes of the Tibetan Plateau are important models for studying the evolution and uplift of the Tibetan Plateau. Examining their adaptation to the high-salt environment is interesting. In this study, we first assembled the RNA-Seq data of each tissue of G. przewalskii, G. selincuoensis, and G. namensis from Qinghai Lake, Selincuo Lake, and Namtso Lake, respectively, obtained by the group previously. After obtaining reliable results, the adaptation of the gills, kidneys, and livers of the three species to the high-salinity environment was assessed by weighted gene co-expression network analysis (WGCNA). Using module eigengenes (ME), 21, 22, and 22 gene modules were identified for G. przewalskii, G. selincuoensis, and G. nemesis, respectively. Functional clustering analysis of genes in the significant association module identified several genes associated with osmolarity-regulated potential KEGG pathways in the gills of three species of Schizothoracine fish. Th17 cell differentiation pathway was up-regulated in the gills of all three species; histocompatibility class 2 II antigen and E alpha (h2-ea) were up-regulated genes in this pathway. Functional clustering analysis of genes in apparently related modules in the kidney unveiled several differential KEGG pathways. The pentose phosphate pathway was up-regulated in the three Schizothoracine fishes, and glucose-6-phosphate dehydrogenase (g6pd) was an up-regulated gene in this pathway. In the livers of the three Schizothorax species, the propanoate metabolism pathway was up-regulated, and succinate-CoA ligase GDP-forming subunit beta (suclg2) was an up-regulated gene in this pathway. The above analyses provide reference data for the adaptation of Schizothorax to high-salt environments and lay the foundation for future studies on the adaptive mechanism of Schizothorax in the plateau. These results partly fill the void in the knowledge gap in the survival adaptations of Schizothoracine fishes to highland saline lakes.

T cell receptor (TCR) engagement triggers T cell responses, yet how TCR-mediated activation is regulated at the plasma membrane remains unclear. Here, we report that deleting the membrane scaffolding protein Flotillin-2 (Flot2) increases T cell antigen sensitivity, resulting in enhanced TCR signaling and effector function in response to weak TCR stimulation. T cell-specific Flot2-deficient mice exhibited reduced tumor growth and enhanced immunity to infection. Flot2-null CD4+ T cells exhibited increased Th1 polarization, proliferation, Nur77 induction, and phosphorylation of ZAP70 and ERK1/2 upon weak TCR stimulation, indicating a sensitized TCR-triggering threshold. Single-cell RNA-Seq suggested that Flot2-null CD4+ T cells follow a similar route of activation as WT CD4+ T cells but exhibit higher occupancy of a discrete activation state under weak TCR stimulation. Given prior reports that TCR clustering influences sensitivity of T cells to stimuli, we evaluated TCR distribution with super-resolution microscopy. Flot2 ablation increased the number of surface TCR nanoclusters on naive CD4+ T cells. Collectively, we posit that Flot2 modulates T cell functionality to weak TCR stimulation, at least in part, by regulating surface TCR clustering. Our findings have implications for improving T cell reactivity in diseases with poor antigenicity, such as cancer and chronic infections.

Periodontitis, a widespread inflammatory disease, is the major cause of tooth loss in adults. While mechanical periodontal therapy benefits the periodontal disease treatment, adjunctive periodontal therapy is also necessary. Topically applied anti-inflammatory agents have gained considerable attention in periodontitis therapy. Although azithromycin (AZM) possesses excellent anti-inflammatory properties, its bioavailability is limited owing to poor water solubility and the absence of sustained release mechanisms. Herein, we synthesized biodegradable microspheres (AZM@PLGA-SF) for sustained AZM release to locally ameliorate periodontal inflammation and facilitate periodontal tissue regeneration. AZM was encapsulated in poly (lactic-co-glycolic acid) (PLGA) microspheres (AZM@PLGA) using single emulsion-solvent evaporation, followed by surface coating with silk fibroin (SF) via electrostatic adsorption, reducing the initial burst release of AZM. In vivo, local treatment with AZM@PLGA-SF microspheres significantly reduced periodontal inflammation and restored periodontal tissue to healthy levels. Mechanically, the formulated microspheres regulated the periodontal inflammatory microenvironment by reducing the levels of pro-inflammatory cytokines (tumor necrosis factor -α, interleukin [IL]-6, interferon-γ, IL-2, and IL-17A) in gingival crevicular fluid and promoted the expression of anti-inflammatory cytokines (IL-4 and IL-10). AZM@PLGA-SF microspheres demonstrated excellent biological safety. Therefore, we introduce an anti-inflammatory therapy for periodontitis with substantial potential for mitigating periodontal inflammation and encouraging the repair and regeneration of periodontal tissues.

As of late, reinvigoration of exhausted T cells as a form of immunotherapy against cancer has been a promising strategy. However, inconsistent results highlight the uncertainties in the current understanding of cellular exhaustion and the need for research and better treatment design. In our previous work, we utilized mathematical modeling and analysis to recapitulate and complement the biological understanding of exhaustion in response to growing tumors. The results of this work recognized that the population size of progenitor exhausted CD8+ T cells played a larger factor in tumor control compared to cytotoxic abilities. From this notion, it was theorized that exhaustion in CD4+ T cells, which are known to help coordinate and promote the size of the CD8+ T cell response, would be a significant component of tumor control. To test this theory, this paper expands on the previous mathematical framework by incorporating CD4+ T cells and the exhaustion they face in response to tumoral settings. Analysis of this model supports our theory, indicating that targeting CD4+ T cell exhaustion would have a potentially large impact on tumor burden and should be investigated along with current immunotherapy strategies of exhausted CD8+ T cell reinvigoration. Ultimately, this work narrows the scope of future research, providing a potential target for improved therapeutic efforts.

This review aims to comprehensively examine the immune response following traumatic brain injury (TBI) and how its disruption can impact healing and recovery.

The immune response is now considered a key element in the pathophysiology of TBI, with consequences far beyond the acute phase after injury. A delicate equilibrium is crucial for a healthy recovery. When this equilibrium is disrupted, chronic inflammation and immune imbalance can lead to detrimental effects on survival and disability. Globally, traumatic brain injury (TBI) imposes a substantial burden in terms of both years of life lost and years lived with disability. Although its epidemiology exhibits dynamic trends over time and across regions, TBI disproportionally affects the younger populations, posing psychosocial and financial challenge for communities and families. Following the initial trauma, the primary injury is succeeded by an inflammatory response, primarily orchestrated by the innate immune system. The inflammasome plays a pivotal role during this stage, catalyzing both programmed cell death pathways and the up-regulation of inflammatory cytokines and transcription factors. These events trigger the activation and differentiation of microglia, thereby intensifying the inflammatory response to a systemic level and facilitating the migration of immune cells and edema. This inflammatory response, initially originated in the brain, is monitored by our autonomic nervous system. Through the vagus nerve and adrenergic and cholinergic receptors in various peripheral lymphoid organs and immune cells, bidirectional communication and regulation between the immune and nervous systems is established.

Head and neck cancer ranks as the sixth most common cancer worldwide, highlighting the critical need for the development of new therapies to enhance treatment efficacy. The activation of innate immune receptors given their potent immune stimulatory properties aid in the eradication of cancer cells. In this study, we investigated the immune mechanism and anti-tumor function of a Toll-like receptor 9 (TLR9) agonist, CpG-oligodeoxynucleotide-2722 (CpG-2722), in combination with cyclic dinucleotides, which are agonists of stimulator of interferon genes (STING). Our results revealed that CpG-2722 stimulation increased the expression of Th1 pro-inflammatory cytokines. Stimulation by STING agonists exhibited lower expression of Th1 cytokines but higher expression of Th2 cytokines compared to CpG-2722. However, the combination of these two agonists significantly enhanced Th1 cytokines while reducing Th2 cytokines. Moreover, in vivo experiment showed that both CpG-2722 and 2'3'-c-di-AMP suppressed head and neck tumor growth, with their combination proving more effective than the use of these agonists alone. The combined treatment cooperatively promoted the production of Th1 cytokines and type I interferons, while suppressing Th2 cytokines in the tumors as observed in vitro. Additionally, it led to the accumulation of M1 macrophages, dendritic cells, and T cells, shaping a favorable tumor microenvironment for T cell-mediated tumor killing. The anti-tumor activity of the CpG-2722 and 2'3'-c-di-AMP combination depends on the macrophage presence but does not directly activate M1 macrophage polarization, instead working through a reprogrammed cytokine profile. Furthermore, this combination shows a cooperative anti-tumor activity with anti-PD-1 in treating head and neck tumors. Overall, these findings highlight a Th response and macrophage phenotype reprograming involved functional mechanism underlying the cooperative activity of the combination of TLR9 and STING agonists in the immunotherapy of head and neck cancer.

Infectious uveitis is a significant cause of visual impairment worldwide, caused by diverse pathogens such as viruses, bacteria, fungi, and parasites. Understanding its prevalence, etiology, pathogenesis, molecular mechanism, and clinical manifestations is essential for effective diagnosis and management.

A systematic literature search was conducted using PubMed, Google Scholar, Web of Science, Scopus, and Embase, focusing on studies published in the last fifteen years from 2009 to 2023. Keywords included "uveitis," "infectious uveitis," "viral uveitis," and others. Rigorous inclusion and exclusion criteria were applied, and data were synthesized thematically. Gene symbols related to infectious uveitis were analyzed using protein-protein interaction (PPI) networks and pathway analyses to uncover molecular mechanisms associated with infectious uveitis.

The search from different databases yielded 97 eligible studies. The review identified a significant rise in publications on infectious uveitis, particularly viral uveitis, over the past fifteen years. Infectious uveitis prevalence varies geographically, with high rates in developing regions due to systemic infections and limited diagnostic resources. Etiologies include viruses (39%), bacteria (17%), and other pathogens, substantially impacting adults aged 20-50 years. Pathogenesis involves complex interactions between infectious agents and the ocular immune response, with key roles for cytokines and chemokines. The PPI network highlighted IFNG, IL6, TNF, and CD4 as central nodes. Enriched pathways included cytokine-cytokine receptor interaction and JAK-STAT signaling. Clinical manifestations range from anterior to posterior uveitis, with systemic symptoms often accompanying ocular signs. Diagnostic strategies encompass clinical evaluation, laboratory tests, and imaging, while management involves targeted antimicrobial therapy and anti-inflammatory agents.

This review underscores the complexity of infectious uveitis, driven by diverse pathogens and influenced by various geographical and systemic factors. Molecular insights from PPI networks and pathway analyses provide a deeper understanding of its pathogenesis. Effective management requires comprehensive diagnostic approaches and targeted therapeutic strategies.

In our study, we investigated the impact of tacrolimus (TAC) on CD4+ T cell subsets in 41 AChR-MG patients over 12 weeks. Twenty-seven patients were classified as the response group (RG) (improved myasthenia gravis composite scores ≥3), while 14 were non-response. We found that TAC treatment significantly reduced Th17 and pathogenic Th17 cells, along with IL-17 levels in RG, while Th1 and Tfh cells slightly decreased without affecting Th2 or Treg subsets. This indicates that TAC's clinical benefits may be due to its inhibitory effect on the Th17 response, enhancing our insight into its immunomodulatory mechanisms in MG management.

Immune-mediated inflammatory disease (IMID) is a complex disorder characterized by excessive immune responses involving T cells and their subsets, leading to direct tissue damage. T cells can be broadly categorized into CD4+ T cells and CD8+ T cells. CD4+ T cells are composed of several subsets, including T helper (Th)1, Th2, Th9, Th17, Th22, follicular helper T cells (Tfhs), and regulatory T cells (Tregs), while effector CD8+ T cells consist mainly of cytotoxic T cells (CTLs). Current therapies for IMID are ineffective, prompting exploration into mesenchymal stem cells (MSCs) as a promising clinical treatment due to their immunomodulatory effects and self-renewal potential. Recent studies have shown that MSCs can suppress T cells through direct cell-to-cell contact or secretion of soluble cytokines. Nevertheless, the precise effects of MSCs on T cell subsets remain inadequately defined. In this review, we summarize the most recent studies that have examined how MSCs modulate one or more effector T-cell subsets and the mechanisms behind these modifications in vitro and several mouse models of clinical inflammation. This also provides theoretical support and novel insights into the efficacy of clinical treatments involving MSCs. However, the efficacy of MSC therapies in clinical models of inflammation varies, showing effective remission in most cases, but also with exacerbation of T-cell-mediated inflammatory damage in some instances.

The most promising method of containing the COVID-19 pandemic is considered to be vaccination against SARS-CoV-2 infection. However, research on the relationship between vaccination against COVID-19 and cancer has primarily examined induced immunity rather than the disease itself. Considering that breast cancer is the most common cancer among women, the main goal of this study was to examine the impact of the Sinopharm and AstraZeneca vaccination on tumor characteristics such as tumor size, important tumor markers, tumor-infiltrating lymphocytes, metastasis to vital organs, and investigation of the PI3K/AKT signaling pathway, and the expression levels of relevant genes (PTEN, mTOR, AKT, PI3K, GSK3, and FoxO1) of the luminal B (MC4L2) mouse model. The tumor size of the mice was measured and monitored every two days, and after thirty days, the mice were euthanized. Remarkably, after vaccination, all vaccinated mice showed a decrease in the size of their tumor and an increase in the number of lymphocytes that had invaded the tumors. Tumor marker levels (VEGF, Ki-67, MMP-2/9), CD4/CD8 ratio, metastasis to vital organs, hormone receptors (ER, PR, and HER-2), and expression of genes related to the advancement of the PI3K/AKT signaling pathway were lower in vaccinated mice. Our research showed that the COVID-19 vaccine can have an anti-cancer effect by slowing the tumor progression and metastasis.