bims-flamet Biomed News
on Cytokines and immunometabolism in metastasis
Issue of 2025–03–02
nineteen papers selected by
Peio Azcoaga, Biodonostia HRI
  1. Tumor-infiltrating myeloid cells; mechanisms, functional significance, and targeting in cancer therapy.
  2. Metabolic regulation of myeloid-derived suppressor cells in tumor immune microenvironment: targets and therapeutic strategies.
  3. CCL20 in the tumor microenvironment: implications for cancer progression and therapeutic approaches.
  4. A new strategy for the treatment of advanced ovarian cancer: utilizing nanotechnology to regulate the tumor microenvironment.
  5. Reprogramming the tumor microenvironment by targeting cytidine deaminase in pancreatic ductal adenocarcinoma tumors: implications for the role of P2Y6 receptors.
  6. Dual-delivery of exosome inhibitor and therapeutic gene via lipid nano-assemblies for tumor immune evasion inhibition.
  7. Advances in small extracellular vesicles: roles in the tumor microenvironment and epithelial ovarian cancer diagnosis and treatment.
  8. Revealing the role of regulatory b cells in cancer: development, function and treatment significance.
  9. Implications of intratumoral microbiota in tumor metastasis: a special perspective of microorganisms in tumorigenesis and clinical therapeutics.
  10. Lipid Metabolism in Breast Cancer: From Basic Research to Clinical Application.
  11. Ferroptosis in Pulmonary Disease and Lung Cancer: Molecular Mechanisms, Crosstalk Regulation, and Therapeutic Strategies.
  12. The role of cytokines in shaping the future of Cancer immunotherapy.
  13. Notch and Hedgehog Signaling Unveiled: Crosstalk, Roles, and Breakthroughs in Cancer Stem Cell Research.
  14. [Research Progress of Tumor-associated Neutrophils 
in the Occurrence and Development of Lung Cancer].
  15. Chimeric Antigen Receptor Cell Therapy: Empowering Treatment Strategies for Solid Tumors.
  16. Breaking Immunosuppression to Enhance Cancer Stem Cell-Targeted Immunotherapy.
  17. Targeting leukocyte immunoglobulin‑like receptor B2 in the tumor microenvironment: A new treatment prospect for solid tumors (Review).
  18. Extracellular Vesicle-Based Strategies for Tumor Immunotherapy.
  19. The m6A revolution: transforming tumor immunity and enhancing immunotherapy outcomes.
  1. Cell Oncol (Dordr). 2025 Feb 25.
    Tumor-infiltrating myeloid cells; mechanisms, functional significance, and targeting in cancer therapy.
    Fatemeh Sadat Toghraie, Maryam Bayat, Mahsa Sadat Hosseini, Amin Ramezani.
      Tumor-infiltrating myeloid cells (TIMs), which encompass tumor-associated macrophages (TAMs), tumor-associated neutrophils (TANs), myeloid-derived suppressor cells (MDSCs), and tumor-associated dendritic cells (TADCs), are of great importance in tumor microenvironment (TME) and are integral to both pro- and anti-tumor immunity. Nevertheless, the phenotypic heterogeneity and functional plasticity of TIMs have posed challenges in fully understanding their complexity roles within the TME. Emerging evidence suggested that the presence of TIMs is frequently linked to prevention of cancer treatment and improvement of patient outcomes and survival. Given their pivotal function in the TME, TIMs have recently been recognized as critical targets for therapeutic approaches aimed at augmenting immunostimulatory myeloid cell populations while depleting or modifying those that are immunosuppressive. This review will explore the important properties of TIMs related to immunity, angiogenesis, and metastasis. We will also document the latest therapeutic strategies targeting TIMs in preclinical and clinical settings. Our objective is to illustrate the potential of TIMs as immunological targets that may improve the outcomes of existing cancer treatments.
    Keywords:  Cancer immunotherapy; Dendritic cells; Macrophages; Myeloid-derived suppressor cells; Neutrophils
    DOI:  https://doi.org/10.1007/s13402-025-01051-y
  2. Theranostics. 2025 ;15(6): 2159-2184
    Metabolic regulation of myeloid-derived suppressor cells in tumor immune microenvironment: targets and therapeutic strategies.
    Hong Wang, Fei Zhou, Wenqing Qin, Yun Yang, Xiaojiaoyang Li, Runping Liu.
      Cancer remains a major challenge to global public health, with rising incidence and high mortality rates. The tumor microenvironment (TME) is a complex system of immune cells, fibroblasts, extracellular matrix (ECM), and blood vessels that form a space conducive to cancer cell proliferation. Myeloid-derived suppressor cells (MDSCs) are abundant in tumors, and they drive immunosuppression through metabolic reprogramming in the TME. This review describes how metabolic pathways such as glucose metabolism, lipid metabolism, amino acid metabolism, and adenosine metabolism have a significant impact on the function of MDSCs by regulating their immunosuppressive activity and promoting their survival and expansion in tumors. The review also explores key metabolic targets in MDSCs and strategies to modulate MDSC metabolism to improve the tumor immune microenvironment and enhance anti-tumor immune responses. Understanding these pathways can provide insight into potential therapeutic targets for modulating MDSC activity and improving outcomes of cancer immunotherapies.
    Keywords:  MDSC; TME; cancer; immunotherapy; metabolism
    DOI:  https://doi.org/10.7150/thno.105276
  3. Clin Transl Oncol. 2025 Feb 22.
    CCL20 in the tumor microenvironment: implications for cancer progression and therapeutic approaches.
    Louis Boafo Kwantwi, James Danquah Boafo, Bevelyn Emefa Egleh, Mingfeng Li.
      Increasing knowledge of the immunosuppressive tumor microenvironment in cancer-related processes has led to the developing of novel immune-based therapies that have changed the cancer treatment paradigm. In the tumor microenvironment, the plethora of soluble factors secreted by tumor cells interacts with immune cells and non-immune components to deliver signals necessary for tumor progression. Accordingly, targeting tumor-derived factors inducing this immunosuppressive tumor microenvironment has become an appealing therapeutic potential in advancing cancer treatment. CCL20, a chemokine best known to induce leucocyte migration in response to pathological and inflammatory conditions, has been implicated in tumor proliferation, angiogenesis, metastasis, immunosuppression, and therapeutic resistance. Notably, CCL20 and its receptor CCR6 are important in tumor microenvironment interactions. This review discusses the interaction between the CCL20-CCR6 axis and the tumor microenvironment and how these interactions promote tumor progression. Also, an outline of studies utilizing CCL20 in combination with other standard cancer treatments has been shed.
    Keywords:  CCL20; CCR6; Endothelial cells; Fibroblast; Immune cells; Tumor cells; Tumor microenvironment
    DOI:  https://doi.org/10.1007/s12094-025-03874-5
  4. Front Immunol. 2025 ;16 1542326
    A new strategy for the treatment of advanced ovarian cancer: utilizing nanotechnology to regulate the tumor microenvironment.
    Zixuan Xiong, Yichun Huang, Shulong Cao, Xuqun Huang, Haiyuan Zhang.
      Advanced ovarian cancer (AOC) is prone to recurrence, which can be attributed to drug resistance. Drug resistance may be related to the tumor microenvironment (TME), including the immune and non-immune TME. In the immune TME, the immune effector cells such as dendritic cells (DCs), M1-like tumor-associated macrophages (M1-TAMs), and T cells are inhibited. In contrast, immunosuppressive cells such as M2-like tumor-associated macrophages (M2-TAMs), myeloid-derived suppressor cells (MDSCs), and regulatory T cells (Tregs) are activated. These changes make it difficult to produce immune effects and affect the efficacy of chemo-immunotherapy. In the non-immune TME, mechanisms such as apoptosis inhibition, DNA damage response (DDR), and epithelial-mesenchymal transition (EMT) can promote tumor growth, metastasis, and drug resistance. Despite the challenges posed by the TME in the treatment of AOC, the unique biological advantages of nanoparticles (NPs) make it possible to regulate the TME. NPs can stimulate the immune responses of M1-TAMs, DCs, and T cells while reducing the infiltration of immune suppressive cells such as M2-TAMs and Tregs, thereby regulating the AOC immune TME. In addition, NPs can regulate the non-immune TME by reducing apoptosis in AOC cells, inhibiting homologous recombination (HR) repair, reversing EMT, and achieving the effect of reversing drug resistance. In summary, the application of NPs provides some new venues for clinical treatment in AOC.
    Keywords:  advanced ovarian cancer (AOC); chemo-immunotherapy; drug resistance; nanotechnology; tumor microenvironment (TME)
    DOI:  https://doi.org/10.3389/fimmu.2025.1542326
  5. Purinergic Signal. 2025 Feb 27.
    Reprogramming the tumor microenvironment by targeting cytidine deaminase in pancreatic ductal adenocarcinoma tumors: implications for the role of P2Y6 receptors.
    Abdel-Aziz S Shatat.
      Immunotherapies, such as immune checkpoint inhibitors (ICI), anti-cancer vaccines and adoptive T cell transfer, are promising treatments for cancer patients. However, ICI have not shown therapeutic benefit for most mismatch repair-proficient colorectal and pancreatic ductal adenocarcinoma tumors (PDAC), which are aggressive and deadly (Li et al. in Biomedicines 12:2175, 2024). Tumor metabolism can enhance immunological tolerance, but hinder immune cell function. In a recent publication in Nature Cancer, Scolaro et al. (Scolaro et al. in Nature Cancer 5:1206-1226, 2024) showed that cytidine deaminase (CDA) upregulation may play a crucial role in shaping the immunosuppressive landscape of human PDAC and other tumors. CDA targeting in pancreatic cancer cell lines led to reduced tumor growth, weight and total regression after treatment aimed at the programmed cell death protein 1 receptor (PD-1) immune checkpoint protein. CDA inhibition, both genetically and pharmacologically, overcame immunotherapy resistance in PDAC models. CDA targeting in PDAC cells altered the tumor microenvironment (TME), enabling T cells to respond to anti-PD-1. In mice with sgNT and sgCda tumors receiving anti-PD-1 treatment, they reduced the number of CD8+ T cells. CDA reduction in cancer cells makes tumors more sensitive to immunotherapy, presumably by overcoming immunosuppressive tumor-associated macrophages (TAMs) and forcing them to adopt an immunostimulatory phenotype. The study also found that cancer cells produce a TME rich in UDP (and UTP) by taking advantage of the CDA-mediated pyrimidine salvage pathway. This setting inhibits the recruitment and activation of CD8+ T cells by promoting the infiltration and immunosuppressive characteristics of P2Y6 receptor-expressing TAMs.
    Keywords:  Cytidine deaminase; Immunotherapy resistance; P2X6 receptor; Pancreatic ductal adenocarcinoma
    DOI:  https://doi.org/10.1007/s11302-025-10071-0
  6. J Control Release. 2025 Feb 22. pii: S0168-3659(25)00178-6. [Epub ahead of print]
    Dual-delivery of exosome inhibitor and therapeutic gene via lipid nano-assemblies for tumor immune evasion inhibition.
    Jaehyun Kim, Minjeong Kim, Heesoo Han, SangJin Kim, Shayan Fakhraei Lahiji, Yong-Hee Kim.
      The tumor microenvironment, with its complex immune evasion mechanisms, significantly hinders the efficacy of anti-tumor immunotherapies, including immune checkpoint inhibitors. Consequently, there is a strong impetus for extensive research to elucidate the immunosuppressive mechanisms within the tumor microenvironment and to develop novel therapeutic strategies. In this study, we have developed a drug/gene delivery system (folate-modified GW4869-loaded siIRF3 nano-complex, FD9R-GW/siIRF3) designed to simultaneously target and inhibit two key immune evasion pathways in the tumor microenvironment. The folate receptor-mediated delivery of GW4869 to cancer cells and tumor-associated macrophages (TAMs) led to the suppression of biosynthesis and release of tumor-derived exosomes (TEXs) containing exosomal PD-L1. Furthermore, IRF3 gene silencing effectively inhibited the M2-type differentiation of TAMs, and suppressed the secretion of CC motif chemokine ligand 22 (CCL22) in cancer cells, consequently reducing the recruitment of regulatory T cells (Tregs). The efficacy of FD9R-GW/siIRF3 in impeding tumor immune evasion was substantiated by an augmented recruitment of cytotoxic T cells and a diminished M2 macrophage polarization in the folate receptor-expressing 4 T1 allograft breast cancer model. Furthermore, the combination of a-PD-1 immunotherapy with FD9R-GW/siIRF3 led to a significant enhancement in the antitumor immune response, as evidenced by the inhibition of circulating tumor-derived exosomal PD-L1.
    Keywords:  Cancer immunotherapy; Exosomal PD-L1; Folate receptor-targeted immunotherapy; IRF3 gene silencing; Tumor-derived exosome blockade
    DOI:  https://doi.org/10.1016/j.jconrel.2025.02.065
  7. Front Oncol. 2025 ;15 1526944
    Advances in small extracellular vesicles: roles in the tumor microenvironment and epithelial ovarian cancer diagnosis and treatment.
    Liang Peng, Yi Lai, Baodi Cao.
      Epithelial ovarian cancer (EOC), one of the most prevalent subtypes of ovarian cancer, has a 5-year survival rate of less than 30%, highlighting the urgent need for novel diagnostic and therapeutic strategies. The tumor microenvironment (TME), a critical regulator of tumor progression, includes various components, among which small extracellular vesicles (sEVs) serve as important molecular carriers, having gained attention as significant contributors to cancer biology. These vesicles, released by cells into the extracellular space, are pivotal in the pathogenesis of EOC. In addition, sEVs show significant promise as biomarkers and therapeutic agents for the treatment and management of this malignancy. This review explores recent advancements in the understanding of sEVs within the TME and their potential applications in the diagnosis and treatment of EOC.
    Keywords:  diagnostic biomarkers; epithelial ovarian cancer; recent advances; small extracellular vesicles; therapeutic strategies; tumor microenvironment
    DOI:  https://doi.org/10.3389/fonc.2025.1526944
  8. Cancer Immunol Immunother. 2025 Feb 25. 74(4): 125
    Revealing the role of regulatory b cells in cancer: development, function and treatment significance.
    Ruyu Ye, Sijia Li, Yuxiao Li, Kaixin Shi, Li Li.
      B cells are essential components of the immune response, primarily recognized for their ability to produce antibodies. However, emerging research reveals their important roles in regulating immune responses and influencing tumor development, independent of antibodies. The connection between tumor progression and alterations in the tumor microenvironment is well-established, as immune infiltrating cells can enhance the survival of tumor cells by modifying their surroundings. Despite this, the majority of studies have focused on T cells and macrophages, creating a gap in our understanding of B cells. Regulatory B cells (Bregs) represent a crucial subpopulation that plays a significant role in maintaining immune balance. They may have a substantial impact on tumor immunity by negatively regulating tumor-infiltrating immune cells. This paper reviews the existing literature on Bregs, examining their development, phenotypes, functions, and the mechanisms through which they exert their regulatory effects. Furthermore, we highlight their potential interventional roles and prognostic significance in cancer therapy. By addressing the current gaps in knowledge regarding Bregs within tumors, we hope to inspire further research that could lead to innovative cancer treatments and improved outcomes for patients.
    Keywords:  Breg cells; Breg development; Breg function; Breg subtypes; Cancer prognosis
    DOI:  https://doi.org/10.1007/s00262-025-03973-w
  9. Front Immunol. 2025 ;16 1526589
    Implications of intratumoral microbiota in tumor metastasis: a special perspective of microorganisms in tumorigenesis and clinical therapeutics.
    Lei Zhang, Xichu Duan, Yanhua Zhao, Dejiu Zhang, Yuan Zhang.
      Tumor metastasis is the main cause of therapeutic failure and mortality in cancer patients. The intricate metastastic process is influenced by both the intrinsic properties of tumor cells and extrinsic factors, such as microorganisms. Notably, some microbiota have been discovered to colonize tumor tissues, collectively known as intratumoral microbiota. Intratumoral microbiota can modulate tumor progression through multiple mechanisms, including regulating immune responses, inducing genomic instability and gene mutations, altering metabolic pathways, controlling epigenetic pathways, and disrupting cancer-related signaling pathways. Furthermore, intratumoral microbiota have been shown to directly impact tumor metastasis by regulating cell adhesion, stem cell plasticity and stemness, mechanical stresses and the epithelial-mesenchymal transition. Indirectly, they may affect tumor metastasis by modulating the host immune system and the tumor microenvironment. These recent findings have reshaped our understanding of the relationship between microorganims and the metastatic process. In this review, we comprehensively summarize the existing knowledge on tumor metastasis and elaborate on the properties, origins and carcinogenic mechanisms of intratumoral microbiota. Moreover, we explore the roles of intratumoral microbiota in tumor metastasis and discuss their clinical implications. Ongoing research in this field will establish a solid foundation for novel therapeutic strategies and clinical treatments for various tumors.
    Keywords:  clinical perspective; intratumoral microbiota; mechanisms; tumor metastasis; tumor pathogenesis
    DOI:  https://doi.org/10.3389/fimmu.2025.1526589
  10. Cancers (Basel). 2025 Feb 14. pii: 650. [Epub ahead of print]17(4):
    Lipid Metabolism in Breast Cancer: From Basic Research to Clinical Application.
    Xiangyu Huang, Bowen Liu, Songjie Shen.
      Breast cancer remains the most prevalent cancer among women globally, with significant links to obesity and lipid metabolism abnormalities. This review examines the role of lipid metabolism in breast cancer progression, highlighting its multifaceted contributions to tumor biology. We discuss key metabolic processes, including fatty acid metabolism, triglyceride metabolism, phospholipid metabolism, and cholesterol metabolism, detailing the reprogramming that occurs in these pathways within breast cancer cells. Alterations in lipid metabolism are emphasized for their roles in supporting energy production, membrane biogenesis, and tumor aggressiveness. Furthermore, we examine how lipid metabolism influences immune responses in the tumor microenvironment, affecting immune cell function and therapeutic efficacy. The potential of lipid metabolism as a target for novel therapeutic strategies is also addressed, with a focus on inhibitors of key metabolic enzymes. By integrating lipid metabolism with breast cancer research, this review underscores the importance of lipid metabolism in understanding breast cancer biology and developing treatment approaches aimed at improving patient outcomes.
    Keywords:  breast cancer; lipid metabolism; reprogramming; targeting therapy
    DOI:  https://doi.org/10.3390/cancers17040650
  11. MedComm (2020). 2025 Mar;6(3): e70116
    Ferroptosis in Pulmonary Disease and Lung Cancer: Molecular Mechanisms, Crosstalk Regulation, and Therapeutic Strategies.
    Dandan Guo, Songhua Cai, Lvdan Deng, Wangting Xu, Sentao Fu, Yaling Lin, Tong Jiang, Qing Li, Zhijun Shen, Jian Zhang, Peng Luo, Bufu Tang, Ling Wang.
      Ferroptosis is a distinct form of iron-dependent programmed cell death characterized primarily by intracellular iron accumulation and lipid peroxidation. Multiple cellular processes, including amino acid metabolism, iron metabolism, lipid metabolism, various signaling pathways, and autophagy, have been demonstrated to influence the induction and progression of ferroptosis. Recent investigations have elucidated that ferroptosis plays a crucial role in the pathogenesis of various pulmonary disorders, including lung injury, chronic obstructive pulmonary disease, pulmonary fibrosis, and asthma. Ferroptosis is increasingly recognized as a promising novel strategy for cancer treatment. Various immune cells within the tumor microenvironment, including CD8+ T cells, macrophages, regulatory T cells, natural killer cells, and dendritic cells, have been shown to induce ferroptosis in tumor cells and modulate the process through the regulation of iron and lipid metabolism pathways. Conversely, ferroptosis can reciprocally alter the metabolic environment, leading to the activation or inhibition of immune cell functions, thereby modulating immune responses. This paper reviews the molecular mechanism of ferroptosis and describes the tumor immune microenvironment, discusses the connection between ferroptosis and the tumor microenvironment in lung cancer and pulmonary diseases, and discusses the development prospect of their interaction in the treatment of lung cancer and pulmonary diseases.
    Keywords:  ferroptosis; immune microenvironment; lung cancer; molecular mechanisms; pulmonary disease
    DOI:  https://doi.org/10.1002/mco2.70116
  12. Cytokine. 2025 Feb 25. pii: S1043-4666(25)00035-3. [Epub ahead of print]189 156888
    The role of cytokines in shaping the future of Cancer immunotherapy.
    Sahar Safaei, AmirHossein Yari, Omid Pourbagherian, Leili Aghebati Maleki.
      As essential immune system regulators, cytokines are essential for modulating both innate and adaptive immunological responses. They have become important tools in cancer immunotherapy, improving the immune system's capacity to identify and destroy tumor cells. This article examines the background, workings, and therapeutic uses of cytokines, such as interleukins, interferons, and granulocyte-macropHage colony-stimulating factors, in the management of cancer. It examines the many ways that cytokines affect immune cell activation, signaling pathways, tumor development, metastasis, and prognosis by modifying the tumor microenvironment. Despite the limited effectiveness of cytokine-based monotherapy, recent developments have concentrated on new fusion molecules such as immunocytokines, cytokine delivery improvements, and combination techniques to maximize treatment efficacy while reducing adverse effects. Current FDA-approved cytokine therapeutics and clinical trial results are also included in this study, which offers insights into how cytokines might be used with other therapies including checkpoint inhibitors, chemotherapy, and radiation therapy to address cancer treatment obstacles. This study addresses the intricacies of cytokine interactions in the tumor microenvironment, highlighting the possibility for innovative treatment methods and suggesting fresh techniques for enhancing cytokine-based immunotherapies. PEGylation, viral vector-mediated cytokine gene transfer, antibody-cytokine fusion proteins (immunocytokines), and other innovative cytokine delivery techniques are among the novelties of this work, which focuses on the most recent developments in cytokine-based immunotherapy. Additionally, the study offers a thorough examination of the little-reviewed topic of cytokine usage in conjunction with other treatment techniques. It also discusses the most recent clinical studies and FDA-approved therapies, providing a modern perspective on the developing field of cancer immunotherapy and suggesting creative ways to improve treatment effectiveness while lowering toxicity. BACKGROUND: Cytokines are crucial in cancer immunotherapy for regulating immune responses and modifying the tumor microenvironment (TME). However, challenges with efficacy and safety have driven research into advanced delivery methods and combination therapies to enhance their therapeutic potential.
    Keywords:  Cancer treatment; Clinical trials; Cytokines; FDA-approved cytokine therapies; Immunotherapy; Tumor microenvironment
    DOI:  https://doi.org/10.1016/j.cyto.2025.156888
  13. Life (Basel). 2025 Feb 04. pii: 228. [Epub ahead of print]15(2):
    Notch and Hedgehog Signaling Unveiled: Crosstalk, Roles, and Breakthroughs in Cancer Stem Cell Research.
    Sabina Iluta, Madalina Nistor, Sanda Buruiana, Delia Dima.
      The development of therapies that target cancer stem cells (CSCs) and bulk tumors is both crucial and urgent. Several signaling pathways, like Notch and Hedgehog (Hh), have been strongly associated with CSC stemness maintenance and metastasis. However, the extensive crosstalk present between these two signaling networks complicates the development of long-term therapies that also minimize adverse effects on healthy tissues and are not overcome by therapy resistance from CSCs. The present work aims to overview the roles of Notch and Hh in cancer outburst and the intersection of the two pathways with one another, as well as with other networks, such as Wnt/β-catenin, TGF, and JAK/STAT3, and to explore the shaping of the tumor microenvironment (TME) with specific influence on CSC development and maintenance.
    Keywords:  Hedgehog signaling; Notch signaling pathway; cancer stem cells; cancer therapy; tumor biology; tumor microenvironment
    DOI:  https://doi.org/10.3390/life15020228
  14. Zhongguo Fei Ai Za Zhi. 2025 Jan 20. 28(1): 55-62
    [Research Progress of Tumor-associated Neutrophils 
in the Occurrence and Development of Lung Cancer].
    Xiaoyan Li, Jianjun Zhou, Chaoting Zhao, Yudi Zhang.
      Lung cancer is the malignant tumor with the highest mortality rate worldwide. The tumor microenvironment (TME) is a key factor in the progression of lung cancer, composed of tumor cells, signaling molecules, fibroblasts, immune cells, etc. Among them, tumor associated neutrophil (TAN), as an important component of immune cells in the TME, plays multiple roles in tumor cell proliferation, invasion, angiogenesis, and metastasis due to its aberrant function, and is closely associated with poor prognosis. However, there are limited researches on the mechanism of TAN in lung cancer. This review aims to provide more scientific basis for studying the therapeutic targets of lung cancer and developing new drugs by elucidating the different subtypes of TAN and their mechanisms of action in the occurrence and development of lung cancer.
.
    Keywords:  Immunity; Lung neoplasms; Tumor microenvironment; Tumor-associated neutrophils
    DOI:  https://doi.org/10.3779/j.issn.1009-3419.2025.101.02
  15. Curr Issues Mol Biol. 2025 Jan 31. pii: 90. [Epub ahead of print]47(2):
    Chimeric Antigen Receptor Cell Therapy: Empowering Treatment Strategies for Solid Tumors.
    Tang-Her Jaing, Yi-Wen Hsiao, Yi-Lun Wang.
      Chimeric antigen receptor-T (CAR-T) cell therapy has demonstrated impressive efficacy in the treatment of blood cancers; however, its effectiveness against solid tumors has been significantly limited. The differences arise from a range of difficulties linked to solid tumors, including an unfriendly tumor microenvironment, variability within the tumors, and barriers to CAR-T cell infiltration and longevity at the tumor location. Research shows that the reasons for the decreased effectiveness of CAR-T cells in treating solid tumors are not well understood, highlighting the ongoing need for strategies to address these challenges. Current strategies frequently incorporate combinatorial therapies designed to boost CAR-T cell functionality and enhance their capacity to effectively target solid tumors. However, these strategies remain in the testing phase and necessitate additional validation to assess their potential benefits. CAR-NK (natural killer), CAR-iNKT (invariant natural killer T), and CAR-M (macrophage) cell therapies are emerging as promising strategies for the treatment of solid tumors. Recent studies highlight the construction and optimization of CAR-NK cells, emphasizing their potential to overcome the unique challenges posed by the solid tumor microenvironment, such as hypoxia and metabolic barriers. This review focuses on CAR cell therapy in the treatment of solid tumors.
    Keywords:  chimeric antigen receptor; invariant natural killer T; macrophage; natural killer; solid tumor; tumor microenvironment
    DOI:  https://doi.org/10.3390/cimb47020090
  16. Int J Biol Sci. 2025 ;21(4): 1819-1836
    Breaking Immunosuppression to Enhance Cancer Stem Cell-Targeted Immunotherapy.
    Fang Zheng, Shan Zhang, Alfred E Chang, James J Moon, Max S Wicha, Shelley Xuelai Wang, Junhui Chen, Jixian Liu, Fanjun Cheng, Qiao Li.
      Cancer stem cell (CSC)-targeted immunotherapy has emerged as a novel strategy in cancer treatment in the past decade. However, its efficacy is significantly limited due to the existence of host immune suppressive activity. Specifically, programmed cell death ligand-1 (PD-L1) is overexpressed in CSCs, and PD-L1 overexpressed CSCs create immunosuppressive milieu via interacting with various immune cells in tumor microenvironments (TME). Hence, novel immunotherapeutic strategies targeting CSCs with concurrent immunosuppression interruption will be promising in enhancing anti-CSC effects. These include dendritic cell (DC) and nanodisc (ND)-based vaccines to present CSC antigens in the forms of CSC lysate, CSC-marker proteins, and CSC-derived peptides to induce anti-CSC immunity. In addition, CSC-directed bispecific antibodies (BiAbs) and antibody drug conjugates (ADCs) have been developed to target CSCs effectively. Furthermore, chimeric antigen receptor (CAR)-T cell therapy and natural killer (NK) cell-based therapy targeting CSCs have achieved progress in both solid and hematologic tumors, and inhibition of CSC associated signaling pathways has proven successful. In this review, we aimed to outline the roles and regulatory mechanisms of PD-L1 in the properties of CSCs; the crosstalk between CSCs and immunosuppressive cells in TME, and recent progress and future promises of immunosuppression blockage to enhance CSC-targeted immunotherapy.
    Keywords:  antibody drug conjugates; bispecific antibodies; cancer stem cells; cancer vaccines; immunosuppression; immunotherapy
    DOI:  https://doi.org/10.7150/ijbs.101025
  17. Oncol Lett. 2025 Apr;29(4): 181
    Targeting leukocyte immunoglobulin‑like receptor B2 in the tumor microenvironment: A new treatment prospect for solid tumors (Review).
    Meng Cao, Jing Luan, Cui Zhai, Huan Liu, Zhenhao Zhang, Na Guo.
      Leukocyte immunoglobulin-like receptor B2 (LILRB2) functions as an immunosuppressive receptor that has a prominent role in immune regulation. The expression of LILRB2 is higher in a variety of solid malignant tumors compared with that in corresponding normal tissues. LILRB2 can be expressed in tumor cells and tumor stromal cells within the tumor microenvironment. Upregulation of LILRB2 in tumors is significantly associated with a poorer tumor phenotype, increased tolerance to certain therapeutic drugs, tumor immune escape and shorter patient overall survival time. Therefore, LILRB2 can be utilized as a novel biomarker to predict the prognosis of patients with solid malignant tumors, and targeting LILRB2 may be an effective strategy for targeted cancer therapy. The present review provides a general overview of the role and mechanisms of LILRB2 in the microenvironment of solid tumors, and emphasizes the significance of targeting LILRB2 as a promising approach for tumor-specific therapy.
    Keywords:  LILRB2; drugs; immune; therapy; tumor microenvironment
    DOI:  https://doi.org/10.3892/ol.2025.14927
  18. Pharmaceutics. 2025 Feb 14. pii: 257. [Epub ahead of print]17(2):
    Extracellular Vesicle-Based Strategies for Tumor Immunotherapy.
    Luksika Jiramonai, Xing-Jie Liang, Mengliang Zhu.
      Immunotherapy is one of the most promising approaches for cancer management, as it utilizes the intrinsic immune response to target cancer cells. Normally, the human body uses its immune system as a defense mechanism to detect and eliminate foreign objects, including cancer cells. However, cancers develop a 'switch off' mechanism, known as immune checkpoint proteins, to evade immune surveillance and suppress immune activation. Therefore, significant efforts have been made to develop the strategies for stimulating immune responses against cancers. Among these, the use of extracellular vesicles (EVs) to enhance the anti-tumor immune response has emerged as a particularly promising approach in cancer management. EVs possess several unique properties that elevate the potency in modulating immune responses. This review article provides a comprehensive overview of recent advances in this field, focusing on the strategic usage of EVs to overcome tumor-induced immune tolerance. We discuss the biogenesis and characteristics of EVs, as well as their potential applications in medical contexts. The immune mechanisms within the tumor microenvironment and the strategies employed by cancers to evade immune detection are explored. The roles of EVs in regulating the tumor microenvironment and enhancing immune responses for immunotherapy are also highlighted. Additionally, this article addresses the challenges and future directions for the development of EV-based nanomedicine approaches, aiming to improve cancer immunotherapy outcomes with greater precision and efficacy while minimizing off-target effects.
    Keywords:  extracellular vesicles; immune checkpoint inhibitors; immune evasion; immunotherapy; tumor microenvironment
    DOI:  https://doi.org/10.3390/pharmaceutics17020257
  19. Cell Biosci. 2025 Feb 22. 15(1): 27
    The m6A revolution: transforming tumor immunity and enhancing immunotherapy outcomes.
    Tongguo Shi, Huan Zhang, Yueqiu Chen.
      N6-methyladenosine (m6A), the most prevalent RNA modification in eukaryotes, plays a critical role in the development and progression of various diseases, including cancer, through its regulation of RNA degradation, stabilization, splicing, and cap-independent translation. Emerging evidence underscores the significant role of m6A modifications in both pro-tumorigenic and anti-tumorigenic immune responses. In this review, we provide a comprehensive overview of m6A modifications and examine the relationship between m6A regulators and cancer immune responses. Additionally, we summarize recent advances in understanding how m6A modifications influence tumor immune responses by directly modulating immune cells (e.g., dendritic cells, tumor-associated macrophages, and T cells) and indirectly affecting cancer cells via mechanisms such as cytokine and chemokine regulation, modulation of cell surface molecules, and metabolic reprogramming. Furthermore, we explore the potential synergistic effects of targeting m6A regulators in combination with immune checkpoint inhibitor (ICI) therapies. Together, this review consolidates current knowledge on the role of m6A-mediated regulation in tumor immunity, offering insights into how a deeper understanding of these modifications may identify patients who are most likely to benefit from immunotherapies.
    Keywords:  Cancer; Immune checkpoint inhibitor; Immunotherapy; N6-methyladenosine (m6A); Tumor immunity
    DOI:  https://doi.org/10.1186/s13578-025-01368-z
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