Bone defects repair continues to be a significant challenge facing the world. Biological scaffolds, bioactive molecules, and cells are the three major elements of bone tissue engineering, which have been widely used in bone regeneration therapy, especially with the rise of bioactive molecules in recent years. According to their physical properties, they can be divided into force, magnetic field (MF), electric field (EF), ultrasonic wave, light, heat, etc. However, the transmission of bioactive molecules has obvious shortcomings that hinder the development of the tissue-rearing process. This paper reviews the mechanism of physical signal induction in bone tissue engineering in recent years. It summarizes the application strategies of physical signal in bone tissue engineering, including biomaterial designs, physical signal loading strategies and related pathways. Finally, the ongoing challenges and prospects for the future are discussed.

Microwave ablation (MWA) triggers a weak systemic immune response that leads to the abscopal regression of distant metastases while killing local tumors, known as the abscopal effect. Combining MWA with chimeric antigen receptor (CAR)-T cells demonstrates promise in enhancing the abscopal effect in antigen-homogeneous tumors. However, the loss of the antigen recognized by CAR or intrinsic antigenic heterogeneity in solid tumors poses a major obstacle. SIRPα variant (CV1)-secreting CAR-T (sCAR-T) cells elicit an abscopal effect on distant tumors with antigen heterogeneity in mice receiving local MWA. Mechanistically, sCAR-T cells can locally eliminate antigen-positive tumors and secrete CV1, whereas the secreted CV1 can activate macrophages that migrate to non-ablated tumor sites in response to post-MWA chemokines, eliciting a macrophage-dependent abscopal effect that enables phagocytosis of antigen-heterogeneous cancer cells. This macrophage-dependent abscopal effect instigated by MWA and sCAR-T cells offers a clinically translatable strategy in metastatic solid tumors with antigen heterogeneity.

Aliya®Pulsed Electric Field (PEF) technology is an emerging strategy in the field of cancer treatment, offering a novel approach to ablation therapy that does not rely on thermal mechanisms. By employing a multi-stage experimental setup, including potato tuber, porcine liver, and murine breast cancer models, we explored the dose-response relationship on ablation and immune modulation by varying the pulse packets delivered from 20 to 100. The biologic response observed with 60 packets represented a minimum effective dose yielding reproducible ablation parameters, immune response, and efficacy which could be augmented with immune checkpoint blockade. This pre-clinical analysis provides a first step toward understanding the therapeutic index for PEF technology beyond ablation, a consideration that will require robust clinical validation in well-designed prospective studies.

Hepatocellular carcinoma (HCC) persists as a leading cause of cancer-related mortality, often diagnosed at advanced stages with limited treatment options. Locoregional therapies (LRTs) are crucial in HCC management, playing significant roles in neoadjuvant and palliative treatments, among others. However, the unique disease background of HCC necessitates multidisciplinary and integrated treatment strategies. The therapeutic landscape for advanced HCC has been significantly broadened by the advent of combined therapies, presenting multiple approaches aimed at improving long-term survival, which remains a critical challenge. This review offers a comprehensive overview of major LRTs for HCC, highlighting recent technological advancements and exploring the challenges and limitations in their application, and presents the latest developments in combination therapies, including combinations between different LRTs and their integration with systemic treatments. Additionally, we outline future directions for the development of integrated treatment modalities for advanced HCC.

Hepatocellular carcinoma (HCC) is a highly immunogenic tumor and the third leading cause of cancer-related deaths worldwide with an increasing incidence. Therefore, the combination of immunotherapy with other approaches, such as anti-angiogenic agents and local area therapy, has become a new strategy for HCC treatment.

We searched PubMed and Web of Science and extracted publications relating to the radiofrequency ablation (RFA) and immunotherapy. The search terms were: "radiofrequency ablation", "immunotherapy" and "hepatocellular carcinoma", and manual searches of eligible articles from literature reference lists were performed. We then thoroughly reviewed the literature on ablation combined with immunotherapy for HCC, analyzed the relevant mechanism, and explored the safety and effectiveness of this form of combination therapy.

RFA combined with immunotherapy in HCC is reported to have good efficacy and controllable safety. On the one hand, RFA can induce the immunogenic substances including Ficolin-3, IL-1 and heat shock protein and regulate the immune cells by mediating the Th1/Th2 ratio, increasing Th17 cells, etc. On the other hand, RFA treatment can lead to tumor immune microenvironment reconstruction, increasing the proportion of functional T cells and upregulate PD-1 in T cells in distant tumors without RFA. This combined strategy has the ability to enhance the anti-tumor immune response through synergies, significantly reduce the risk of recurrence and improve survival.

RFA combined with immunotherapy yields a good synergistic effect: it can further strengthen anti-tumor response, delay distant tumor growth, reduce tumor recurrence and metastasis, providing new options for HCC systemic treatment.

For medically inoperable non-small cell lung cancer, microwave ablation (MWA) represents a super minimally invasive alternative treatment. However, tumor recurrence remains a concern. Here, it is demonstrated that the combination of MWA with Flt3L significantly inhibits tumor recurrence by CD8+ central memory T (TCM)-like cell-dependent antitumor immune responses within the tumor-draining lymph nodes (TdLN). TdLN-TCM-like cells encompassed both tumor-specific memory T (TTSM) and progenitor-exhausted T (TPEX) cells. The expansion of these cells markedly altered the differentiation of exhausted T cells within the tumor microenvironment (TME). TPEX predominantly differentiated into transitory effector-like exhausted T cells (TEX-int). The expansion of TTSM cells elicited by the combined therapy was reliant on conventional dendritic cells (cDCs) and was likely specifically dependent on the migratory cDC1s (Mig cDC1s) within the TdLN. The upregulation of ICOSL on migratory cDC1s was pivotal in initiating TTSM-like cell-mediated antitumor responses. Slc38a2 may be a critical gene responsible for the upregulation of ICOSL in Mig cDC1s following combined treatment. Finally, the combined treatment significantly enhanced the antitumor efficacy of immunotherapy based on PD-1 blockade. The research thereby afforded a novel strategic approach to forestall tumor recurrence after MWA therapy, while also providing the foundational proof-of-concept for impending clinical investigations.

Pharmacological studies have shown that the rhizome of Atractylodes macrocephala Koidz. (Compositae), commonly known as atractylodes macrocephala rhizome (AMR), can modulate immunity. Nevertheless, its resources have been largely depleted, and the pharmacological activity of artificial AMR is relatively modest. We hypothesized that the fermented crude extracts of the rhizosphere fungi of AMR would have similar immunomodulatory effects since the metabolites generated by these fungi are similar to those of the host plant given their long-term synergistic evolution.

Rhizosphere fungi were isolated from the rhizosphere soil of AMR and cultured to produce the secondary metabolites. These metabolites were then sequentially extracted with four solvents of increasing polarities (petroleum ether, ethyl acetate, n-butanol, and water). The in vitro immunomodulatory activities of the metabolite extracts were evaluated by cell proliferation capacity, cell phagocytosis activity, NO secretion capacity, cell morphology changes, and cytokine (TNF-α, IL-1β and IL-6) secretion capacity in RAW264.7 macrophage cells. The biologically active secondary metabolites produced by the rhizosphere fungi were identified using ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS).

Three rhizosphere fungi, namely Penicillium (MK-1), Penicillium glaucoroseum (MN-1), and Purpureocillium lilalium (MG-1), were isolated from the rhizosphere soil of AMR. The assays for cell proliferation capacity, cell phagocytosis activity, and NO secretion capacity showed that all metabolite extracts exhibited in vitro immunomodulatory activities. The crude extracts of MG-1 exhibited the highest levels of in vitro immunomodulatory activities compared to the other extracts. Furthermore, it was demonstrated that the fermented extracts of MG-1 could facilitate immunological enhancement in vitro by altering the cellular morphology in the resting state and increasing the secretions of TNF-α, IL-1β, and IL-6. Meanwhile, there was no observable endotoxin contamination. The metabolite profiling of MG-1 by UHPLC-Q-TOFMS revealed the presence of several compounds with established immunoreactive activities, including L-arginine, prostaglandin I2, deoxyguanosine, bestatin, and osthole.

The present study demonstrated that the metabolite extracts of the rhizosphere fungi isolated from the rhizosphere soil of AMR exhibited in vitro immunoreactive activities and that these rhizosphere fungi could produce several bioactive metabolites. The crude extracts of the rhizosphere fungi may hence extend the medicinal utility of AMR and provide a basis for further development of natural plant-based immunomodulators.

Nasal carcinomas in dogs are locally invasive neoplasms with a low metastatic rate that pose significant treatment challenges due to their location and aggressiveness. This study evaluates the safety, feasibility, and therapeutic outcomes of computed tomography-guided radiofrequency ablation (CT-guided RFA) in 15 dogs diagnosed with nasal adenocarcinoma. All patients underwent staging and histopathological diagnosis before treatment. CT-guided RFA achieved a significant tumor volume reduction (82.8%) and improvement in clinical signs such as nasal discharge, epistaxis, and respiratory distress, without complications. Post-RFA CT examinations demonstrated a significant decrease in Hounsfield units and tumor volume. This study has shown that CT-guided RFA is an effective cytoreductive option for minimally invasive management of nasal adenocarcinomas in dogs, particularly when traditional therapies like radiation therapy or surgery are not feasible.

Among all malignant gynecological tumors, ovarian cancer (OC) has the highest mortality rate. OC is often diagnosed at advanced and incurable stages; however, early diagnosis can enable the use of optimized and personalized treatments. Intensive research into the synthesis and characterization of gold nanoparticles (AuNPs) has been performed with the aim of developing innovative materials for use in biological and photothermal therapies for OC. AuNPs can be chemically modified and functionalized by binding to a variety of organic compounds and biomolecules, such as peptides, antibodies and therapeutic agents, via simple synthetic processes. They are particularly suitable for use as carriers for drug delivery. In the present review, the synthesis and characteristics of AuNPs are summarized, and their potential in OC therapy are discussed.

Objective: Immune checkpoint inhibition (ICI) has significantly advanced the field of immuno-oncology, yet not all patients benefit from this therapy. Combining ICI with other therapeutic modalities, including tumor ablation, is currently being explored as a method to enhance ICI efficacy. Mechanical High-Intensity Focused Ultrasound (M-HIFU) represents a promising tumor ablative therapy, inducing cavitation within the tumor, resulting in tumor cell destruction and the release of danger signals and tumor antigens, two key factors contributing to anti-tumor immune responses.

Methods/Results: Preclinical studies on the impact of M-HIFU on the anti-tumor immune response are guiding the translational application of this technique in the clinical setting. This review provides a comprehensive overview of the current understanding of the effects of M-HIFU on the immune system. We report on the effect of M-HIFU on soluble immune modulators and immune cells in different preclinical models, and potential contributions to the anti-tumor immune response. We discuss clinical studies applying M-HIFU and studies that have combined ICI with other ablative therapies to draw parallels to clinical implementation of M-HIFU. Further, we will highlight essential questions that should be addressed in future clinical trials exploring the combination of M-HIFU and ICI in the clinical setting.

Conclusion: Overall, this review offers guidance for the clinical implementation of combining M-HIFU with ICI and highlights key questions that remain to be addressed in first clinical studies.

In recent years, with the continuous development of molecular immunology, immune checkpoint inhibitors (ICIs) have also been widely used in the treatment of gastric cancer, but they still face some challenges: The first is that only some people can benefit, the second is the treatment-related adverse events (TRAEs) that occur during treatment, and the third is the emergence of varying degrees of drug resistance with long-term use. How to overcome these challenges, combined therapy based on ICIs has become one of the important strategies. This article summarizes the clinical application of ICIs combined with chemotherapy, targeted therapy, radiotherapy, photodynamic therapy, thermotherapy, immune adjuvant, and dual immunotherapy and discusses the mechanism, and also summarizes the advantages and disadvantages of the current combination modalities and the potential research value. The aim of this study is to provide more and more optimized combination regimen for ICI combined therapy in patients with advanced gastric cancer and to provide reference for clinical and scientific research.

Immune response is known to play an important role in local tumor control especially in renal cell carcinoma (RCC), which is considered highly immunogenic. For localized tumors, operative resection or local ablative procedures such as cryoablation are common therapeutical options. For thermal ablative procedures such as cryoablation, additional immunological anti-tumor effects have been described.The purpose of this prospective study was to determine changes in peripheral blood circulating lymphocytes and various of their subsets in RCC patients treated with cryoablation or surgery in a longitudinal approach using extensive flow cytometry. Additionally, lymphocytes of RCC patients were compared to a healthy control group.We included 25 patients with RCC. Eight underwent cryoablation and 17 underwent surgery. Univariate and multivariable analysis revealed significantly lower values of B cells, CD4 and CD8 T cells, and various of their subsets in the treatment groups versus the healthy control group. Comparing the two different therapeutical approaches, a significant decline of various lymphocyte subsets with a consecutive normalization after three months was seen for the surgery group, whereas cryoablation led to increased values of CD69 + CD4 + and CD69 + CD8 + cell counts as well as memory CD8 + cells after three months.Treatment-naïve RCC patients showed lower peripheral blood lymphocyte counts compared to healthy controls. The post-treatment course revealed different developments of lymphocytes in the surgery versus cryoablation group, and only cryoablation seems to induce a sustained immunological response after three months.

Immunotherapy has enhanced breast cancer outcomes, but optimizing combination therapies is crucial. Integrating additional treatment modalities, like physical therapies, holds promise for optimizing efficacy. Pan et al. recently reported that combining preoperative immunotherapy with microwave ablation is safe and feasible in early-stage breast cancer, effectively sensitizing peripheral CD8+ T cells.1.

This literature explores the immunostimulatory effects of thermal ablation in the tumor microenvironment, elucidating the mechanisms such as immunogenic cell death, tumor-specific antigens, and damage-associated molecular patterns. Furthermore, it outlines critical issues associated with thermal ablation-induced immunostimulatory challenges and offers insights into future research avenues and potential therapeutic strategies.

Thermal ablation modalities (cryoablation, radiofrequency ablation, and microwave ablation) have long been noted to occasionally induce a systemic antitumoral response. With the widespread use of checkpoint inhibitors, there is a significant interest in whether thermal ablation can promote immune system tumor recognition and increase checkpoint inhibitor response rates. In this review, we examine the current state of preclinical and clinical evidence examining the combination of checkpoint inhibitor therapies and thermal ablation modalities as well as discuss remaining the unanswered questions and directions for future research.

Interventional immuno-oncology is making strides in locoregional therapies to address complex tumor microenvironments. Long-standing interventional radiology cancer therapies, such as tumor ablation and embolization, are being recharacterized in the context of immunotherapy. Intratumoral injections, such as those of genetically engineered or unaltered viruses, and the delivery of immune cells, antibodies, proteins, or cytokines into targeted tumors, along with advancements in delivery techniques, have produced promising results in preliminary studies, indicating their antitumor effectiveness. Emerging strategies using DNA scaffolding, polysaccharides, glycan, chitosan, and natural products are also showing promise in targeted cancer therapy. The future of interventional immuno-oncology lies in personalized immunotherapies that capitalize on individual immune profiles and tumor characteristics, along with the exploration of combination therapies. This study will review various interventional immuno-oncology strategies and emerging technologies to enhance delivery of therapeutics and response to immunotherapy.

The aim of the work described here was to investigate the relative contribution of subtotal ultrasound-guided percutaneous microwave ablation (MWA) to amplifying programmed cell death protein-1 (PD-1) inhibition in advanced hepatocellular carcinoma (HCC).

Between April 2019 and December 2021, advanced HCC patient demographics, tumor response, survival data, neutrophil-to-lymphocyte ratio (NLR) and peripheral lymphocyte profiles were retrospectively collected and analyzed. In hepa1-6 tumor-bearing C57BL/6J mice, RNA sequencing, flow cytometry, immunohistochemistry staining and cytokine tests were also performed.

Twenty-nine HCC patients were enrolled, with a median follow-up duration of 15.1 mo. Compared with the ablation rate (AR) ≤50% group (n = 10), the AR >50% group (n = 19) had a higher disease control rate, a longer time to progression and a longer overall survival. More patients in the AR >50% group had an early decrease in NLR and better immune activation. RNA sequencing of murine tumors subjected to MWA >50% AR showed that immune-related gene expression upregulated. CD8+ T cells, interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) were also increased, indicating that MWA >50% AR boosted the immunomodulatory effect of PD-1 inhibitors.

More MWA could induce superior antitumor immunity by enhancing immune-related gene expression, priming CD8+ T cells and thereby boosting PD-1 inhibition. It is advisable that eradication of tumors to the degree possible should be considered within technical access to obtain a better prognosis.

Microwave ablation (MWA) is an effective treatment for liver cancer (LC), but its impact on distant tumors remains to be fully elucidated. This study investigated the abscopal effects triggered by MWA treatment of LC, at different power levels and with or without combined immune checkpoint inhibition (ICI). We established a mouse model with bilateral subcutaneous LC and applied MWA of varied power levels to ablate the right-sided tumor, with or without immunotherapy. Left-sided tumor growth was monitored to assess the abscopal effect. Immune cell infiltration and distant tumor neovascularization were quantified via immunohistochemistry, revealing insights into the tumor microenvironment and neovascularization status. Th1- and Th2-type cytokine concentrations in peripheral blood were measured using ELISA to evaluate systemic immunological changes. It was found that MWA alone, especially at lower power, promoted distant tumor growth. On the contrary, combining high-power MWA with anti-programmed death (PD)-1 therapy promoted CD8+ T-cell infiltration, reduced regulatory T-cell infiltration, upregulated a Th1-type cytokine (TNF-α) in peripheral blood, and inhibited distant tumor growth. In summary, combining high-power MWA with ICI significantly enhances systemic antitumor immune responses and activates the abscopal effect, offering a facile and robust strategy for improving treatment outcomes.

EUS-guided radiofrequency ablation (EUS-RFA) has been performed as an alternative to surgery for the treatment of pancreatic tumors. The promising results obtained using this procedure suggest that the indication for EUS-RFA could be expanded to the management of extrapancreatic tumors. Here, we evaluate the feasibility, efficacy, and safety of EUS-RFA in the treatment of left adrenal tumors.

This single-center, prospective study was conducted at Asan Medical Center between January 2016 and November 2021. A total of 11 patients with left adrenal tumors were enrolled in the study. The technical success rate, treatment response, and adverse events were evaluated.

EUS-RFA was performed successfully in all patients (technical success rate, 100%). The indications for the procedure were an increase in tumor size (n = 8), and adrenal tumor with adrenal hormone excess (n = 3). After a median of 2 EUS-RFA sessions (range, 1-2), 73% of patients had a complete response, and 27% had a partial response. During follow-up, 5 patients experienced self-limiting mild abdominal pain; no moderate or severe adverse events were reported.

EUS-RFA showed high technical feasibility, clinical success, and an acceptable safety profile in the treatment of left adrenal tumors. In patients at high surgical risk, EUS-RFA can be considered as an alternative therapeutic modality to surgery for the treatment of left adrenal tumors.

Although systemic immunotherapy has achieved durable responses and improved survival for certain patients and cancer types, low response rates and immune system-related systemic toxicities limit its overall impact. Intratumoral (intralesional) delivery of immunotherapy is a promising technique to combat mechanisms of tumor immune suppression within the tumor microenvironment and reduce systemic drug exposure and associated side effects. However, intratumoral injections are prone to variable tumor drug distribution and leakage into surrounding tissues, which can compromise efficacy and contribute to toxicity. Controlled release drug delivery systems such as in situ-forming hydrogels are promising vehicles for addressing these challenges by providing improved spatio-temporal control of locally administered immunotherapies with the goal of promoting systemic tumor-specific immune responses and abscopal effects. In this review we will discuss concepts, applications, and challenges in local delivery of immunotherapy using controlled release drug delivery systems with a focus on intratumorally injected hydrogel-based drug carriers.

Primary liver cancer, of which around 75-85% is hepatocellular carcinoma in China, is the fourth most common malignancy and the second leading cause of tumor-related death, thereby posing a significant threat to the life and health of the Chinese people.

Since the publication of Guidelines for Diagnosis and Treatment of Primary Liver Cancer in China in June 2017, which were updated by the National Health Commission in December 2019, additional high-quality evidence has emerged from researchers worldwide regarding the diagnosis, staging, and treatment of liver cancer, that requires the guidelines to be updated again. The new edition (2022 Edition) was written by more than 100 experts in the field of liver cancer in China, which not only reflects the real-world situation in China but also may reshape the nationwide diagnosis and treatment of liver cancer.

The new guideline aims to encourage the implementation of evidence-based practice and improve the national average 5-year survival rate for patients with liver cancer, as proposed in the "Health China 2030 Blueprint."

Endoscopic radiofrequency ablation (RFA) has emerged as a minimally invasive treatment option in cases of malignant biliary obstruction, pancreatic cancer, and other pancreatic cystic neoplasms. Intraductal biliary RFA is safe, effective, and confers a survival advantage over stenting alone, where it should be used an adjunct to biliary stenting. Endoscopic ultrasound-guided RFA can also provide pancreatic cyst resolution in patients who are not ideal operative candidates. The aim of this review is to describe the endoscopic applications and associated outcomes of RFA.

The aim of our study was to evaluate, under real-life conditions, survival of patients with advanced HCC (BCLC-C), either initially presenting in that stage or migrating from BCLC-A to BCLC-C within 2 years after curative LR/RFA, treated either with Atezolizumab-Bevacizumab or TKIs.

Sixty-four cirrhotic patients with advanced HCC, who either initially presented as BCLC-C and were treated with Atezo-Bev (group A, N = 23) or TKIs (group B, N = 15) or who migrated from BCLC-A to BCLC-C stage within 2 years after LR/RFA and were either treated with Atezo-Bev (group C, N = 12) or TKIs (group D, N = 14), were retrospectively evaluated.

The four groups were comparable for all baseline parameters (demographics/platelets/liver disease etiology/diabetes/varices/Child-Pugh stage/ALBI grade) except for CPT score and MELD-Na. Using Cox-regression analysis, we observed that survival of group C after systemic treatment onset was significantly higher compared to group A (HR 3.71, 1.20-11.46, p = 0.02) and presented a trend to statistical significance when compared to group D (HR 3.14, 0.95-10.35, p = 0.06), adjusted for liver disease severity scores. When all BCLC-C patients classified as such due to PS only were excluded from the study, a trend for the same survival benefit in group C was shown, even in the most difficult-to-treat population with extrahepatic disease or macrovascular invasion.

Cirrhotic patients with advanced HCC initially diagnosed in BCLC-C, exhibit the worst survival irrespective of treatment schedule, whereas patients progressing to BCLC-C following disease recurrence after LR/RFA, seem to mostly benefit from Atezo-Bev, even patients with extrahepatic disease and/or macrovascular invasion. Liver disease severity seems to drive survival of these patients.

In patients with liver malignancies, the cellular immune function was impaired in vitro after selective internal radiotherapy (SIRT). Because immunosuppression varied substantially, in the current study, we investigated in 25 SIRT patients followed up for ten years whether the lymphocyte function was correlated with survival. Peripheral blood mononuclear cells were stimulated with four microbial antigens (tuberculin, tetanus toxoid, Candida albicans and CMV) before therapy and at four time points thereafter, and lymphocyte proliferation was determined by H3-thymidine uptake. The median sum of the responses to these four antigens decreased from 39,464 counts per minute (CPM) increment (range 1080-204,512) before therapy to a minimum of 700 CPM increment on day 7 after therapy (0-93,187, p < 0.0001). At all five time points, the median survival in patients with weaker responses was 2- to 3.5-fold shorter (p < 0.05). On day 7, the median survival in patients with responses below and above the cutoff of a 2 CPM increment was 185 and 523 days, respectively (χ2 = 9.4, p = 0.002). In conclusion, lymphocyte function could be a new predictor of treatment outcome after SIRT.

Cancer immunotherapy is an innovative treatment strategy to enhance the ability of the immune system to recognize and eliminate cancer cells. However, dose limitations, low response rates, and adverse immune events pose significant challenges. To address these limitations, gold nanoparticles (AuNPs) have been explored as immunotherapeutic drug carriers owing to their stability, surface versatility, and excellent optical properties. This review provides an overview of the advanced synthesis routes for AuNPs and their utilization as drug carriers to improve precision therapies. The review also emphasises various aspects of AuNP-based immunotherapy, including drug loading, targeting strategies, and drug release mechanisms. The application of AuNPs combined with cancer immunotherapy and their therapeutic efficacy are briefly discussed. Overall, we aimed to provide a recent understanding of the advances, challenges, and prospects of AuNPs for anticancer applications.

Multimode thermal therapy (MTT) is an innovative interventional therapy developed for the treatment of liver malignancies. When compared to the conventional radiofrequency ablation (RFA), MTT typically offers improved prognosis for patients. However, the effect of MTT on the peripheral immune environment and the mechanisms underlying the enhanced prognosis have yet to be explored. The aim of this study was to further investigate the mechanisms responsible for the difference in prognosis between the two therapies.

In this study, peripheral blood samples were collected from four patients treated with MTT and two patients treated with RFA for liver malignancies at different time points before and after the treatment. Single cell sequencing was performed on the blood samples to compare and analyze the activation pathways of peripheral immune cells following the MTT and RFA treatment.

There was no significant effect of either therapy on the composition of immune cells in peripheral blood. However, the differential gene expression and pathway enrichment analysis demonstrated enhanced activation of T cells in the MTT group compared to the RFA group. In particular, there was a remarkable increase in TNF-α signaling via NF-κB, as well as the expression of IFN-α and IFN-γ in the CD8⁺ effector T (CD8⁺ Teff) cells subpopulation, when compared to the RFA group. This may be related to the upregulation of PI3KR1 expression after MTT, which promotes the activation of PI3K-AKT-mTOR pathway.

This study confirmed that MTT could more effectively activate peripheral CD8⁺ Teff cells in patients compared with RFA and promote the effector function, thus resulting in a better prognosis. These results provide a theoretical basis for the clinical application of MTT therapy.

Energy-based focal therapy (FT) uses targeted, minimally invasive procedures to destroy tumors while preserving normal tissue and function. There is strong emerging interest in understanding how systemic immunity against the tumor can occur with cancer immunotherapy, most notably immune checkpoint inhibitors (ICI). The motivation for combining FT and ICI in cancer management relies on the synergy between the two different therapies: FT complements ICI by reducing tumor burden, increasing objective response rate, and reducing side effects of ICI; ICI supplements FT by reducing local recurrence, controlling distal metastases, and providing long-term protection. This combinatorial strategy has shown promising results in preclinical study (since 2004) and the clinical trials (since 2011). Understanding the synergy calls for understanding the physics and biology behind the two different therapies with distinctive mechanisms of action. In this review, we introduce different types of energy-based FT by covering the biophysics of tissue-energy interaction and present the immunomodulatory properties of FT. We discuss the basis of cancer immunotherapy with the emphasis on ICI. We examine the approaches researchers have been using and the results from both preclinical models and clinical trials from our exhaustive literature research. Finally, the challenges of the combinatory strategy and opportunities of future research is discussed extensively.

Personalized cancer treatments help to deliver tailored and biologically driven therapies for cancer patients. Interventional oncology techniques are able to treat malignancies in a locoregional fashion, with a variety of mechanisms of action leading to tumor necrosis. Tumor destruction determines a great availability of tumor antigens that can be recognized by the immune system, potentially triggering an immune response. The advent of immunotherapy in cancer care, with the introduction of specific immune checkpoint inhibitors, has led to the investigation of the synergy of these drugs when used in combination with interventional oncology treatments. The aim of this paper is to review the most recent advances in the field of interventional oncology locoregional treatments and their interactions with immunotherapy.

Microwave ablation can produce immune activation due to thermal effects. However, the nonthermal effects of microwaves on the immune system are still largely unexplored. In this study, we sequentially exposed rats to 1.5 GHz microwave for 6 min and 2.8 GHz microwave for 6 min at an average power density of 5, 10, and 30 mW/cm². The structure of the thymus, spleen, and mesenteric lymph node were observed, and we showed that multifrequency microwave exposure caused tissue injuries, such as congestion and nuclear fragmentation in lymphocytes. Ultrastructural injuries, including mitochondrial swelling, mitochondrial cristae rupture, and mitochondrial cavitation, were observed, especially in the 30 mW/cm² microwave-exposed group. Generally, multifrequency microwaves decreased white blood cells, as well as lymphocytes, monocytes, and neutrophils, in peripheral blood, from 7 d to 28 d after exposure. Microwaves with an average density of 30 mW/cm² produced much more significant inhibitory effects on immune cells. Moreover, multifrequency microwaves at 10 and 30 mW/cm², but not 5 mW/cm², reduced the serum levels of several cytokines, such as interleukin-1 alpha (IL-1α), IL-1β, interferon γ (IFN-γ) and tumor necrosis factor α (TNF-α), at 7 d and 14 d after exposure. We also found similar alterations in immunoglobulins (Igs), IgG, and IgM in serum. However, no obvious changes in complement proteins were detected. In conclusion, multifrequency microwave exposure of 1.5 GHz and 2.8 GHz caused both structural injuries of immune tissues and functional impairment in immune cells. Therefore, it will be necessary to develop an effective strategy to protect people from multifrequency microwave-induced immune suppression.

To establish molecular magnetic resonance (MR) imaging instruments for in vivo characterization of the immune response to hepatic radiofrequency (RF) ablation using cell-specific immunoprobes.

Seventy-two C57BL/6 wild-type mice underwent standardized hepatic RF ablation (70 °C for 5 minutes) to generate a coagulation area measuring 6-7 mm in diameter. CD68+ macrophage periablational infiltration was characterized with immunohistochemistry 24 hours, 72 hours, 7 days, and 14 days after ablation (n = 24). Twenty-one mice were subjected to a dose-escalation study with either 10, 15, 30, or 60 mg/kg of rhodamine-labeled superparamagnetic iron oxide nanoparticles (SPIONs) or 2.4, 1.2, or 0.6 mg/kg of gadolinium-160 (160Gd)-labeled CD68 antibody for assessment of the optimal in vivo dose of contrast agent. MR imaging experiments included 9 mice, each receiving 10-mg/kg SPIONs to visualize phagocytes using T2∗-weighted imaging in a horizontal-bore 9.4-T MR imaging scanner, 160Gd-CD68 for T1-weighted MR imaging of macrophages, or 0.1-mmol/kg intravenous gadoterate (control group). Radiological-pathological correlation included Prussian blue staining, rhodamine immunofluorescence, imaging mass cytometry, and immunohistochemistry.

RF ablation-induced periablational infiltration (206.92 μm ± 12.2) of CD68+ macrophages peaked at 7 days after ablation (P < .01) compared with the untreated lobe. T2∗-weighted MR imaging with SPION contrast demonstrated curvilinear T2∗ signal in the transitional zone (TZ) (186 μm ± 16.9), corresponsing to Iron Prussian blue staining. T1-weighted MR imaging with 160Gd-CD68 antibody showed curvilinear signal in the TZ (164 μm ± 3.6) corresponding to imaging mass cytometry.

Both SPION-enhanced T2∗-weighted and 160Gd-enhanced T1-weighted MR imaging allow for in vivo monitoring of macrophages after RF ablation, demonstrating the feasibility of this model to investigate local immune responses.

Cell death and injury at the site of tumor ablation attracts macrophages. We sought to understand the status and activity of these cells while focusing on transforming growth factor-β1 (TGF-β1), a potent immunosuppressive and tumorigenic cytokine. Patients with urothelial cancer who underwent ablation using electrocautery or laser demonstrated increased infiltration and numbers of CD8+ T cells, along with FoxP3+ regulatory T cells, CD68+ macrophages and elevated levels of TGF-β1 in recurrent tumors. Similar findings were reproduced in a mouse model of urothelial cancer (MB49) by partial tumor ablation with irreversible electroporation (IRE). Stimulation of bone marrow derived macrophages with MB49 cell debris produced using IRE elicited strong M2 polarization, with exuberant secretion of TGF-β1. The motility, phenotypic markers and cytokine secretion by macrophages could be muted by treatment with Pirfenidone (PFD), a clinically approved drug targeting TGF-β1 signaling. MB49 cancer cells exposed to TGF-β1 exhibited increased migration, invasiveness and upregulation of epithelial-mesenchymal transition markers α-Smooth Muscle Actin and Vimentin. Such changes in MB49 cells were reduced by treatment with PFD even during stimulation with TGF-β1. IRE alone yielded better local tumor control when compared with control or PFD alone, while also reducing the overall number of lung metastases. Adjuvant PFD treatment did not provide additional benefit under in vivo conditions.

Microwave ablation has been one form of thermal ablation in treatments for many tumors, which can locally control unresectable tumors. Ferroptosis is iron-dependent cell death caused by the cumulative reactive oxygen species and lipid peroxidation products. Recently, increasing evidence has shown that ferroptosis might play a vital role in MWA-induced tumor suppression. In this article, we briefly illustrate the concept of ferroptosis, the related signal pathways and inducers, the basic principle of microwave ablation in killing tumors, and the key molecules released after microwave ablation. Then, we describe the cross-talking molecules between microwave ablation and ferroptosis, and discussed the potential mechanism of microwave ablation-induced ferroptosis. This review explores the therapeutic target of ferroptosis in enhancing the systemic antitumor effect after microwave ablation, providing theoretical support in combinational microwave ablation with pro-ferroptosis therapy.