bims-carter Biomed News
on CAR-T Therapies
Issue of 2025–05–25
sixteen papers selected by
Luca Bolliger, lxBio
  1. Engineered CAR-NK Cells for Cancer Immunotherapy: Lentiviral-Based CAR Transduction of NK-92 Cells.
  2. Recent advances of chimeric antigen receptor T-cell therapy for acute myeloid leukemia.
  3. Nanomaterial assisted natural killer cell therapy.
  4. Revolutionizing Autoimmune Kidney Disease Treatment with Chimeric Antigen Receptor-T Cell Therapy.
  5. Research trends in CAR-T cell therapy: A comprehensive bibliometric analysis highlighting cardiovascular toxicity and clinical implications.
  6. CAR-NK's balancing act: when scFv affinity is not too tight, not too loose… but just right?
  7. Age-associated nicotinamide adenine dinucleotide decline drives CAR-T cell failure.
  8. Optimized GMP-grade production of non-viral Sleeping Beauty-generated CARCIK cells for enhanced fitness and clinical scalability.
  9. From induced pluripotent stem cell (iPSC) to universal immune cells: literature review of advances in a new generation of tumor therapies.
  10. Advancing cancer gene therapy: the emerging role of nanoparticle delivery systems.
  11. Scalable and ultrafast CAR-T cell production using microfluidics.
  12. A Digital Microfluidic Platform for the Microscale Production of Functional Immune Cell Therapies.
  13. In vivo CAR engineering for immunotherapy.
  14. The Potential Role of CAR T Cell Therapy in Autoimmune Diseases.
  15. Mechanisms of CD8+ T cell exhaustion and its clinical significance in prognosis of anti-tumor therapies: A review.
  16. Practical Guide to Clinical Trial Accessibility: Making Trial Participation a Standard of Care.
  1. Methods Mol Biol. 2025 ;2930 267-275
    Engineered CAR-NK Cells for Cancer Immunotherapy: Lentiviral-Based CAR Transduction of NK-92 Cells.
    Dayane Schmidt, Mariane Cariati Tirapelle, Sima Ebrahimabadi, Alison Felipe Bordini Biggi, Matheus Henrique Dos Santos, Mara Elisama da Silva-Januário, Virginia Picanço E Castro.
      Chimeric antigen receptor (CAR)-T cell therapy has emerged as a groundbreaking immunotherapeutic approach to cancer treatment. However, despite its remarkable results, challenges persist, such as manufacturing complexity, side effects, and cost. Allogeneic therapies offer potential solutions to these challenges by enhancing accessibility, reducing cost, and increasing scalability. Due to their innate cytotoxicity and reduced risks of side effects to the patients, natural killer cells are an up-and-coming option for allogeneic CAR therapy. The NK-92 cell line use allows large-scale expansion suitable for clinical grade applications, providing a uniform and highly cytotoxic source. Nevertheless, gene delivery using viral vectors is still an obstacle related to CAR-NK therapies due to their natural antiviral activity. Thus, the present protocol offers an efficient approach for CAR-NK-92 cell generation via lentiviral transduction, thereby advancing the potential of this promising cancer therapy.
    Keywords:  CAR-NK; Chimeric antigen receptor; Immunotherapy; Lentiviral transduction; NK-92 cells; Viral vector
    DOI:  https://doi.org/10.1007/978-1-0716-4558-1_19
  2. Front Immunol. 2025 ;16 1572407
    Recent advances of chimeric antigen receptor T-cell therapy for acute myeloid leukemia.
    Yang Liu, Wanting Wang, Chaofan Wang, Jun Deng, Yu Hu, Heng Mei, Shanshan Luo.
      Acute myeloid leukemia (AML) is a heterogeneously primary hematopoietic neoplasm characterized by uncontrolled proliferation of immature myeloid cells, which is characterized with poor outcomes. Despite tremendous advances in the treatment paradigm of AML in the past several decades, the cure and prognosis remain unfavorable. More effective treatments are therefore needed to improve the clinical outcomes. Among newly emerging immunotherapies, chimeric antigen receptor (CAR)-T cell immunotherapy is an exceedingly promising approach that has remarkably improved the overall survival for patients with AML. However, current CAR-T cell therapy for AML faces numerous significant challenges such as the identification of truly AML-specific surface antigens, the on-target/off-tumor toxicity, and the immunosuppressive microenvironment of AML. In order to conquer these limitations, novel strategies to advance CAR-T therapy are urgently needed. In this comprehensive review, we summarize the current status of immunotherapy, especially CAR-T cell therapy, highlight the outcomes of current trials and the limitations of CAR-T immunotherapy, hopefully to provide novel insights into the future directions of CAR-T cells in AML.
    Keywords:  acute myeloid leukemia; adoptive cell therapy; chimeric antigen receptor T cell; immunosuppressive microenvironment; immunotherapy
    DOI:  https://doi.org/10.3389/fimmu.2025.1572407
  3. Front Immunol. 2025 ;16 1558701
    Nanomaterial assisted natural killer cell therapy.
    Xuan Yu, Xiaobo Chen, Yanlong Yang, Yingsong Tian, Jie Jia, Xinghe Tong.
      The rising incidence of cancer has heightened interest in immune cell therapy, particularly the role of natural killer (NK) cells, which are essential components of the immune system. Their applications in tumor treatment have expanded significantly, especially with the incorporation of nanomaterials. This review comprehensively examines NK cell biology, encompassing aspects such as classification, distribution, receptor activation, and mechanisms of cytotoxicity. It also explores various NK cell therapies, including their sources, methods of acquisition, expansion techniques, Chimeric antigen receptor-Natural Killer cell (CAR-NK) technology, gene editing strategies, and combination therapies. Additionally, the review discusses the utilization of nanomaterials in NK cell therapy, focusing on nanoparticle-assisted immune regulation and the modulation of the tumor microenvironment. While NK cell therapy holds promise, CAR-NK technology presents certain limitations. The integration of nanomaterials offers potential strategies to enhance therapeutic efficacy. Future research should prioritize the optimization of NK cell therapy, address the limitations associated with CAR-NK technology, investigate the mechanisms of nanomaterials, and develop more effective nanomaterials to improve clinical outcomes.
    Keywords:  CAR-NK; NK cell therapy; nanometer material; natural killer cells; tumor immunotherapy
    DOI:  https://doi.org/10.3389/fimmu.2025.1558701
  4. Research (Wash D C). 2025 ;8 0712
    Revolutionizing Autoimmune Kidney Disease Treatment with Chimeric Antigen Receptor-T Cell Therapy.
    Rui Gu, Jiayi Shen, Jiayu Zhang, Jianhua Mao, Qing Ye.
      Autoimmune kidney diseases (AIKDs) depict a range of disorders involving immune-mediated damage to the kidneys, where conventional biologic therapies involving monoclonal antibodies often prove insufficient because of persistent autoreactive B cell reservoirs in lymphoid organs and inflammatory tissues. The appearance of chimeric antigen receptor (CAR)-T cell therapies targeting B cells has shown transformative potential, with recent clinical trials showing the remarkable efficacy of anti-CD19 CAR-T cells in achieving profound B cell depletion, reducing immune complex deposition, and ameliorating renal inflammation in AIKDs. While these results highlight the potential of CAR-T cell therapy in facilitating immune reset and overcoming treatment resistance, further clinical investigations are imperative to establish its long-term safety and sustained therapeutic benefits. This review synthesizes current evidence on CAR-T cell applications in AIKDs, discusses critical considerations for clinical translation, identifies existing limitations and challenges, and proposes strategic directions for therapeutic optimization and advancement.
    DOI:  https://doi.org/10.34133/research.0712
  5. Medicine (Baltimore). 2025 May 16. 104(20): e42314
    Research trends in CAR-T cell therapy: A comprehensive bibliometric analysis highlighting cardiovascular toxicity and clinical implications.
    Daniyal Ameen, Ehsan Amini-Salehi, Sandeep Samethadka Nayak, Ashraf Ahmed, Alexis Pudimat, Amir Nasrollahizadeh, Kaveh Hosseini, Seyedeh Fatemeh Hosseini Jebelli, Azin Alizadeh Asl, Anthony Loc Nguyen.
       BACKGROUND: Chimeric antigen receptor T cell (CAR-T) therapy is an innovation in oncology, which provides targeted treatment alternatives for certain tumors. CAR-T therapy has been associated to adverse cardiovascular consequences despite its potential for therapeutic benefit. As research in this field expands rapidly, a bibliometric study is needed to map the current state of knowledge and highlight emerging areas of interest to guide future studies and optimize patient outcomes.
    METHODS: A comprehensive bibliometric analysis was conducted using the Web of Science Core Collection and PubMed to examine the literature on CAR-T cell therapy and its cardiovascular implications.
    RESULTS: The annual number of publications on CAR-T therapy and cardiovascular symptoms has steadily increased, experiencing a significant surge starting in 2018. The USA, China, and Germany emerged as the leading contributors. Key journals included Frontiers in Immunology and Blood, while highly cited journals were Lancet Oncology and the Journal of Clinical Oncology. Keyword analysis identified multiple myeloma, immunotherapy, and cytokine release syndrome as major research themes. The clustered map highlighted interconnected research areas, with a significant focus on multiple myeloma, combination therapy, cardiovascular magnetic resonance assessment, and novel therapeutic approaches.
    CONCLUSION: This bibliometric analysis provided a detailed overview of the research landscape on CAR-T cell therapy and its cardiovascular implications, identifying trends and gaps in knowledge. Recent research trends highlighted bispecific antibodies, CAR-T cell therapy, cardiovascular events, lymphoma, management, and outcomes as emerging focus areas. These keywords underscore the developing field of cardiac events, management, and outcomes in patients undergoing CAR-T cell therapy.
    Keywords:  CAR-T cell therapy; bibliometric analysis; cardiotoxicity; cardiovascular implications; immunotherapy; multiple myeloma; research trend
    DOI:  https://doi.org/10.1097/MD.0000000000042314
  6. J Immunother Cancer. 2025 May 21. pii: e012139. [Epub ahead of print]13(5):
    CAR-NK's balancing act: when scFv affinity is not too tight, not too loose… but just right?
    Yanling Liao, Mitchell S Cairo.
      Chimeric antigen receptor (CAR) therapies have revolutionized cancer treatment by enabling immune cells to target tumor cells with high specificity. While extensive research has focused on optimizing single-chain variable fragment (scFv) affinity in CAR-T cells, its impact on CAR-natural killer (NK) cell function remains less understood. A recent study by Rahnama et al, published in the Journal for ImmunoTherapy of Cancer, addresses this gap by investigating how fine-tuning scFv affinity influences CAR-NK efficacy against acute myeloid leukemia. The study demonstrates that lower-affinity 7G3-based CAR-NK cells exhibit superior antigen discrimination, prolonged persistence, and enhanced tumor control compared with their high-affinity counterparts. However, findings with 26292-based CAR-NK cells reveal a more complex, context-dependent relationship between scFv affinity and cytotoxic function. These results highlight the need for individualized optimization of CAR designs, considering factors such as epitope accessibility, ligand-binding kinetics, and cellular context. Future studies incorporating real-time kinetic analyses and tumor microenvironment modeling will be crucial for refining CAR-NK therapies. Striking the right balance between binding affinity, dwell time, and serial killing capacity could enhance CAR-NK therapeutic potential while minimizing toxicity risks.
    Keywords:  Chimeric antigen receptor - CAR; Natural killer - NK
    DOI:  https://doi.org/10.1136/jitc-2025-012139
  7. Nat Cancer. 2025 May 20.
    Age-associated nicotinamide adenine dinucleotide decline drives CAR-T cell failure.
    Helen Carrasco Hope, Jana de Sostoa, Pierpaolo Ginefra, Massimo Andreatta, Yi-Hsuan Chiang, Catherine Ronet, Christine Pich-Bavastro, Jesús Corria Osorio, François Kuonen, Johan Auwerx, Patrizia D'Amelio, Ping-Chih Ho, Santiago J Carmona, George Coukos, Denis Migliorini, Nicola Vannini.
      Chimeric antigen receptor (CAR) T cell therapy is one of the most promising cancer treatments. However, different hurdles are limiting its application and efficacy. In this context, how aging influences CAR-T cell outcomes is largely unknown. Here we show that CAR-T cells generated from aged female mice present a mitochondrial dysfunction derived from nicotinamide adenine dinucleotide (NAD) depletion that leads to poor stem-like properties and limited functionality in vivo. Moreover, human data analysis revealed that both age and NAD metabolism determine the responsiveness to CAR-T cell therapy. Targeting NAD pathways, we were able to recover the mitochondrial fitness and functionality of CAR-T cells derived from older adults. Altogether, our study demonstrates that aging is a limiting factor to successful CAR-T cell responses. Repairing metabolic and functional obstacles derived from age, such as NAD decline, is a promising strategy to improve current and future CAR-T cell therapies.
    DOI:  https://doi.org/10.1038/s43018-025-00982-7
  8. J Transl Med. 2025 May 19. 23(1): 559
    Optimized GMP-grade production of non-viral Sleeping Beauty-generated CARCIK cells for enhanced fitness and clinical scalability.
    Ilaria Pisani, Giusi Melita, Patricia Borges de Souza, Stefania Galimberti, Angela Maria Savino, Jolanda Sarno, Beatrice Landoni, Stefano Crippa, Elisa Gotti, Carolina Cuofano, Olga Pedrini, Chiara Capelli, Giada Matera, Daniela Belotti, Stefania Cesana, Benedetta Cabiati, Michele Quaroni, Valentina Colombo, Massimiliano Mazza, Barbara Vergani, Anna Gaimari, Fabio Nicolini, Marcella Tazzari, Martine Bocchini, Marta Serafini, Alessandro Rambaldi, Benedetta Rambaldi, Giuseppe Dastoli, Andrea Biondi, Giuseppe Gaipa, Martino Introna, Josée Golay, Sarah Tettamanti.
       BACKGROUND: Strict adherence to GMP guidelines and regulatory compliance is crucial when transitioning from research to clinical-grade production of ATMPs like CAR T cells. The success of CAR T cell therapy in treating hematological malignancies highlights the need for closed or automated systems to ensure quality and efficacy. Recent evidence also suggests that ex vivo culture conditions can significantly impact CAR T cell functionality.
    METHODS: We present our optimized methodology for expanding Sleeping Beauty transposon-engineered Chimeric Antigen Receptor-Cytokine-Induced Killer (CARCIK) cells using G-Rex devices and evaluate its impact on CARCIK cell phenotype and T cell fitness.
    RESULTS: Building on our previously validated protocol, we introduced key simplifications to optimize the CARCIK differentiation process. Delaying the nucleofection step eliminated the need for feeder cells while maintaining efficient CAR expression and high cell viability. Transitioning from T-flasks to G-Rex bioreactors reduced operator hands-on time from 21 to 28 days to 14-17 days and resulted in a less differentiated CARCIK cell product. Metabolic and transcriptional analyses showed that the novel protocol improves CARCIK cell fitness and in vivo efficacy against B-cell lymphoma. The novel method was validated in Good Manufacturing Practices (GMP) conditions at our two Cell Factories and yielded enough numbers of CARCIK-CD19 cells for clinical use.
    CONCLUSIONS: Optimizing non-viral CARCIK cell production using G-Rex bioreactors and refined timing adjustments has streamlined the workflow, enhanced cell fitness, and resulted in a highly effective therapeutic product with demonstrated in vivo efficacy in mice. These improvements reduced manipulation and contamination risks, while optimizing logistics and space efficiency, facilitating allogeneic CARCIK generation for a current phase I/II clinical trial (NCT05869279) in patients with R/R CD19 + non-Hodgkin Lymphoma (B-cell NHL) and Chronic Lymphocytic Leukemia (CLL), confirming the approach's scalability and clinical potential.
    Keywords:  CAR T cells; Good manufacturing practices (GMP); Hematological malignancies; Sleeping beauty transposon; T cell fitness; Workflow optimization
    DOI:  https://doi.org/10.1186/s12967-025-06416-3
  9. Transl Cancer Res. 2025 Apr 30. 14(4): 2495-2507
    From induced pluripotent stem cell (iPSC) to universal immune cells: literature review of advances in a new generation of tumor therapies.
    Jing Zhang, Zixuan Jia, Huixin Pan, Wen Ma, Youhan Liu, Xuewen Tian, Yang Han, Qinglu Wang, Caixia Zhou, Jing Zhang.
       Background and Objective: Tumor therapy is still a tough clinical challenge, and cancer immunotherapy has drawn increasing attention. T cells and natural killer (NK) cells play crucial roles in the immune response. Induced pluripotent stem cell (iPSC) technology opens up a new way to produce functionally improved universal iPSC-derived chimeric antigen receptor (CAR) T (CAR-iT) and iPSC-derived CAR-NK (CAR-iNK) cells. This study aims to comprehensively review the generation and clinical applications of iPSC-derived universal CAR-iT and CAR-iNK cells to explore their potential and future directions in cancer immunotherapy.
    Methods: We searched EBSCO, PubMed, and Web of Science databases for relevant literature from 1975 to 2024 on the transformation of iPSCs into universal immune cells.
    Key Content and Findings: iPSC technology enables the generation of enhanced CAR-iNK cells. Genetic modifications can boost the antitumor activity of iPSC-derived immune cells. CAR-iT cells have cytotoxicity issues. In contrast, CAR-iNK cells have advantages as they can be sourced from different origins and enhanced via genetic engineering.
    Conclusions: This review outlines iPSC technology's application in oncology, iNK cells' properties, and the pros and cons of CAR cells in cancer treatment. It also focuses on the current clinical status and modification strategies of CAR-iT and CAR-iNK therapies, facilitating the development of future effective off-the-shelf blood cell therapies.
    Keywords:  Induced pluripotent stem cell technology (iPSC technology); chimeric antigen receptor T cells (CAR-T); chimeric antigen receptor-natural killer (CAR-NK); tumor therapies
    DOI:  https://doi.org/10.21037/tcr-24-1087
  10. J Nanobiotechnology. 2025 May 20. 23(1): 362
    Advancing cancer gene therapy: the emerging role of nanoparticle delivery systems.
    Maoze Wang, Huina Liu, Jinling Huang, Ting Cai, Zhi Ping Xu, Lingxiao Zhang.
      Gene therapy holds immense potential due to its ability to precisely target oncogenes, making it a promising strategy for cancer treatment. Advances in genetic science and bioinformatics have expanded the applications of gene delivery technologies beyond detection and diagnosis to potential therapeutic interventions. However, traditional gene therapy faces significant challenges, including limited therapeutic efficacy and the rapid degradation of genetic materials in vivo. To address these limitations, multifunctional nanoparticles have been engineered to encapsulate and protect genetic materials, enhancing their stability and therapeutic effectiveness. Nanoparticles are being extensively explored for their ability to deliver various genetic payloads-including plasmid DNA, messenger RNA, and small interfering RNA-directly to cancer cells. This review highlights key gene modulation strategies such as RNA interference, gene editing systems, and chimeric antigen receptor (CAR) technologies, alongside a diverse array of nanoscale delivery systems composed of polymers, lipids, and inorganic materials. These nanoparticle-based delivery platforms aim to improve targeted transport of genetic material into cancer cells, ultimately enhancing the efficacy of cancer therapies.
    Keywords:  CAR technologies; Cancer gene therapy; Gene editing; Nanoparticles
    DOI:  https://doi.org/10.1186/s12951-025-03433-8
  11. Lab Chip. 2025 May 21.
    Scalable and ultrafast CAR-T cell production using microfluidics.
    Vladislav Markelov, Konstantin V Arabuli, Ivan Gaponenko, Vladislav Sergeev, Alena Shakirova, Kirill V Lepik, Alexander D Kulagin, Mikhail V Zyuzin.
      Chimeric antigen receptor T cell (CAR-T) therapy has recently gained recognition as a transformative treatment of cancer, particularly of hematological malignancies. However, CAR-T manufacturing remains a major bottleneck of this treatment modality; in standard cases, it takes up to two weeks, resulting in a phenotypic shift toward terminally differentiated T-cells and a significant depletion of T-cells with naive-like phenotype (Tnlp), crucial for sustained clinical efficacy. Leveraging the current progress in microfluidic technologies, we develop and optimize a microfluidic device (MFD) for CAR-T cell production via an ultrafast protocol that integrates T-cell activation and lentiviral transduction in a single step within 24 hours. The MFD geometry allowed reaching a transduction rate of 27% (for MOI 3) compared to 17% and 8% transduction (MOI 3) in 48- and 6-well plates, respectively, used as controls. Notably, in the ultrafast protocol in our MFD, the amount of CD3+ Tnlp is approximately six times higher than that remaining after the standard 9 day protocol (18.07 ± 6.03% vs. 3.97 ± 2.37%). A similar pattern is noted for CD4+ and CD8+ Tnlp, with percentages of 11.07 ± 6.08% vs. 3.56 ± 3.52% and 29.2 ± 7.11% vs. 4.18 ± 1.69%, respectively, in the final CAR-T product. Our results highlight MFDs as a scalable platform to streamline CAR-T manufacturing, with the potential to improve clinical accessibility and outcomes by reducing the production time while preserving essential T-cell phenotypes.
    DOI:  https://doi.org/10.1039/d5lc00139k
  12. Anal Chem. 2025 May 19.
    A Digital Microfluidic Platform for the Microscale Production of Functional Immune Cell Therapies.
    Samuel R Little, Niloufar Rahbari, Mehri Hajiaghayi, Fatemeh Gholizadeh, Fanny-Mei Cloarec-Ung, Joel Phillips, Hugo Sinha, Alison Hirukawa, David J H F Knapp, Peter J Darlington, Steve C C Shih.
      Genetically engineering human immune cells has been shown to be an effective approach for developing novel cellular therapies to treat a wide range of diseases. To expand the scope of these cellular therapies while solving persistent challenges, extensive research and development is still required. Here we use a digital microfluidic enabled electroporation system (referred to as triDrop) specifically designed to mitigate harm during electroporation procedures and compare against two state-of-the-art commercially available systems for the engineering of primary human T cells. We describe the ability to use triDrop for highly efficient transfection with minimal reagent consumption while preserving a healthy transcriptomic profile. Finally, we show for the first time the ability to use a digital microfluidic platform for the miniaturized production of Chimeric Antigen Receptor (CAR) T cell therapies demonstrating how this novel system can lead to a 2-fold improvement in immunotherapeutic functionality compared to gold standard methods while providing up to a 20-fold reduction in cost. These results highlight the potential power of this system for automated, rapid, and affordable next-generation cell therapy R&D.
    DOI:  https://doi.org/10.1021/acs.analchem.4c06911
  13. Nat Rev Immunol. 2025 May 16.
    In vivo CAR engineering for immunotherapy.
    Yan-Ruide Li, Yichen Zhu, Tyler Halladay, Lili Yang.
      Chimeric antigen receptor (CAR)-engineered immune cell therapy represents an important advance in cancer treatments. However, the complex ex vivo cell manufacturing process and stringent patient selection criteria curtail its widespread use. In vivo CAR engineering is emerging as a promising off-the-shelf therapy, providing advantages such as streamlined production, elimination of patient-specific manufacturing, reduced costs and simplified logistics. A large set of preclinical findings has inspired further investigation into treatments for hard-to-treat diseases such as solid tumours and has facilitated the development of advanced products to enhance in vivo CAR engineering efficacy, the persistence of the cellular therapeutic and safety. In this Review, we summarize current in vivo CAR engineering strategies, including nanoparticle-based and viral delivery systems as well as bioinstructive implantable scaffolds, and discuss their advantages and disadvantages. Additionally, we provide a systematic comparison between in vivo and conventional ex vivo CAR engineering methods and address the challenges and future prospects of in vivo CAR engineering.
    DOI:  https://doi.org/10.1038/s41577-025-01174-1
  14. Int J Rheum Dis. 2025 May;28(5): e70192
    The Potential Role of CAR T Cell Therapy in Autoimmune Diseases.
    Jie-Fu Zheng, Yeak-Wun Quek, James Cheng-Chung Wei.
      
    Keywords:  CAR T cell therapy; idiopathic inflammatory myositis; rheumatoid arthritis; systemic lupus erythematosus; systemic sclerosis
    DOI:  https://doi.org/10.1111/1756-185X.70192
  15. Int Immunopharmacol. 2025 May 19. pii: S1567-5769(25)00833-1. [Epub ahead of print]159 114843
    Mechanisms of CD8+ T cell exhaustion and its clinical significance in prognosis of anti-tumor therapies: A review.
    Anrui Yang, Meng Zhou, Yixuan Gao, Ying Zhang.
      In recent years, immunotherapy has gradually become one of the main strategies for cancer treatment, with immune checkpoint inhibitors (ICIs) offering new possibilities for tumor therapy. However, some cancer patients exhibit low responses and resistance to ICIs treatment. T cell exhaustion, a process associated with tumor progression, refers to a subset of T cells that progressively lose effector functions and exhibit increased expression of inhibitory receptors. These exhausted T cells are considered key players in the therapeutic efficacy of immune checkpoint inhibitors. Therefore, understanding the impact of T cell exhaustion on tumor immunotherapy and the underlying mechanisms is critical for improving clinical treatment outcomes. Several elegant studies have provided insights into the prognostic value of exhausted T cells in cancers. In this review, we highlight the process of exhausted T cells and its predictive value in various cancers, as well as the relevant mechanisms behind it, providing new insights into the immunotherapy of cancer.
    Keywords:  CD8(+) T cell exhaustion; Immune cells; Immune checkpoint inhibitors; Review; Tumor microenvironment
    DOI:  https://doi.org/10.1016/j.intimp.2025.114843
  16. Am Soc Clin Oncol Educ Book. 2025 Jun;45(3): e100052
    Practical Guide to Clinical Trial Accessibility: Making Trial Participation a Standard of Care.
    Hedyeh Ebrahimi, Jodie Allen, Yelak Biru, Ravin Garg, Christine Hodgdon, William K Oh, David Steensma, Sumanta K Pal, Therese Mulvey.
      Despite being a cornerstone of cancer treatment advancement, clinical trials remain inaccessible for many patients because of structural, socioeconomic, and systemic barriers. In this multidisciplinary perspective piece, stakeholders from patient advocacy, community oncology, industry, and academic medicine offer a collaborative overview of key challenges and practical solutions to improve trial accessibility. Patient advocates highlight the need to address language barriers, financial toxicity, and underrepresentation through community engagement and patient-centered trial design. Community oncologists underscore infrastructure limitations, generalist practice burdens, and misaligned trial offerings, calling for eligibility reform and cooperative trial models. Industry partners examine how overly restrictive criteria and inconsistent protocol practices hinder diversity and propose portfolio-wide strategies, such as protocol watch lists, for inclusive design. Academic oncologists focus on trial complexity, investigator burden, and limited generalizability, advocating for pragmatic and decentralized trial paradigms. Together, these perspectives underscore the shared responsibility across sectors to modernize clinical trial design, reduce access barriers, and ensure that trial participation becomes a standard and equitable component of cancer care.
    DOI:  https://doi.org/10.1200/EDBK-25-100052
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