The study utilized humanized NOG-EXL mice, a sophisticated transgenic model engineered to express human IL-3 and GM-CSF and reconstituted with human CD34+ hematopoietic stem cells. This model supports the engraftment of both lymphoid and myeloid lineages, faithfully recapitulating key aspects of human immunity, thus enabling rigorous evaluation of CAR-T cell function under conditions mimicking the human immune response. By orthotopically implanting BT972 glioma stem cell (GSC) xenografts into these mice, researchers established a robust platform to monitor tumor dynamics and immune-mediated clearance.

Importantly, the experimental design encompassed intracranial administration of either untransduced control T cells or GPNMB-specific CAR-T cells in multiple dosing rounds. Bioluminescence imaging (BLI) provided non-invasive, real-time assessment of tumor burden, revealing that four of six mice treated with GPNMB CAR-T cells showed profound tumor regression relative to controls. This was particularly notable given that some of the largest tumors exhibited complete or near-complete eradication, underscoring the potency of the GPNMB-targeting strategy.

Flow cytometric analysis further confirmed that GPNMB CAR-T cells effectively recognize and eliminate GPNMB-expressing myeloid cells. The use of U937 macrophage-like cells exposed to various conditioning stimuli demonstrated a marked upregulation of GPNMB at the cell surface, suggesting these tumor-associated macrophages (TAMs) within the glioma microenvironment are susceptible targets. The cytotoxicity assays substantiated that GPNMB CAR-T cells induce specific lysis of these conditioned macrophages, indicating a dual targeting mechanism that attacks both malignant tumor cells and the immunomodulatory macrophage populations that sustain tumor growth.

In co-culture systems incorporating GBM8 glioma stem cells, U937 macrophages, and CAR-T cells, the selective depletion of both GSCs and myeloid cells by GPNMB CAR-T cells resulted in significantly diminished viability of tumor and suppressive macrophage populations. This highlights the therapeutic potential of dual-targeting CAR-T cells to disrupt the tumor-supportive niche and facilitate a more enduring anti-tumor immune response.

Animal survival and tumor progression studies in NSG mice further reinforced the clinical promise of this approach. Co-inoculation of glioma cells with immunosuppressive, cytokine-conditioned U937 macrophages simulated a more physiologically relevant microenvironment, which ordinarily promotes tumor growth and immune evasion. Yet, intracranial administration of GPNMB CAR-T cells significantly inhibited tumor progression and extended survival, surpassing outcomes seen with untransduced T-cell controls.

Multiplex immunofluorescence examination of endpoint brain tissues from treated mice revealed near-complete clearance of GPNMB-positive tumor cells, alongside a substantial reduction in GPNMB+IBA1+ macrophages, indicating successful targeting of TAMs within the TME. The increase in GFP+ CAR-T cells post-treatment suggested effective trafficking and persistence within intracranial tumor sites, a critical factor for durable therapeutic effects.

A fascinating insight emerged from the immunophenotyping of tumor-associated macrophages after CAR-T therapy. Despite the elimination of GPNMB+ tumor cells, CD163+ macrophages persisted in treated lesions and displayed elevated expression of CD206, a scavenger receptor linked to active phagocytosis and efferocytosis. This finding suggests that TAMs contribute to the clearance of tumor debris and may engage in remodeling the immune landscape following CAR-T cell therapy, possibly promoting a shift in macrophage phenotypes.

Further examination detected increased intracellular GPNMB foci within TAMs, concurrent with abundant IFNγ expression, indicating a likely mechanism of macrophage activation and involvement in post-treatment immune responses. These observations hint at a sophisticated crosstalk where CAR-T cell-mediated tumor cell lysis facilitates macrophage phagocytosis, thereby enhancing anti-tumor immunity through secondary immune cell engagement.

The implications of this research are vast, suggesting that dual targeting of tumor cells and their supportive myeloid compartments with GPNMB CAR-T cells represents a promising strategy for treating glioblastoma. By circumventing the immunosuppressive barriers embedded within the GBM microenvironment and directly eliminating key cellular players, this approach may pave a new path toward sustained remission in a disease historically marked by poor prognosis.

Overall, the integration of advanced humanized mouse models, refined immunotherapeutic engineering, and comprehensive spatial and functional analyses provides a compelling framework for future clinical applications. Subsequent trials and exploration into combinatorial regimens may further enhance the efficacy and safety profile of GPNMB CAR-T cell therapies, offering hope for patients battling this formidable malignancy.

This investigation not only advances our understanding of glioblastoma biology but also underscores the potential of CAR-T cell therapies to remodel complex tumor environments. The capacity to concurrently target malignant cells and tumor-associated immune cells heralds a next-generation paradigm in precision oncology, emphasizing multifunctional immunotherapeutic designs as the future of cancer treatment innovation.

As research continues, deciphering the dynamic interactions between CAR-T cells, tumor cells, and myeloid populations will be paramount to optimizing therapeutic durability and overcoming resistance mechanisms. The distinctive dual-targeting modality described here exemplifies the strategic ingenuity required to translate laboratory breakthroughs into tangible clinical success stories against aggressive brain tumors.

Subject of Research:
Dual targeting of glioblastoma tumor and myeloid cells using GPNMB CAR-T cells.

Article Title:
Dual tumour–myeloid targeting of glioblastoma with GPNMB CAR-T cells.

Article References:
Savage, N., Grewal, S., Shaikh, M.V. et al. Dual tumour–myeloid targeting of glioblastoma with GPNMB CAR-T cells. Nature (2026). https://doi.org/10.1038/s41586-026-10641-1

Image Credits:
AI Generated

DOI:
https://doi.org/10.1038/s41586-026-10641-1

Glioblastoma represents the most common malignant primary brain tumor in adults and is characterized by rapid progression and widespread infiltration. Despite aggressive treatment modalities, including surgery, radiation, and chemotherapy, recurrence is almost inevitable, with median survival after relapse rarely exceeding a year. Traditional systemic therapies often falter against GBM because the blood-brain barrier limits drug and immune cell access, while the tumor microenvironment is adept at subverting immune responses through a range of immunosuppressive mechanisms.

The novel CAR T cell therapy explored by Penn researchers targets two distinct antigens on GBM tumor cells, aiming to enhance tumor recognition and eradication capabilities. Unlike conventional CAR T approaches used in hematological malignancies, this therapy is infused via intracerebroventricular (ICV) injection straight into the CSF bathing the brain. This delivery bypasses the restrictive blood-brain barrier, allowing direct contact with tumor sites and enabling unprecedented real-time monitoring of immune responses through sequential CSF sampling.

Employing advanced single-cell RNA sequencing, the research team meticulously analyzed CSF immune cell populations before treatment and at intervals post-infusion—specifically at days seven and twenty-one. This granular cellular profiling revealed a consistent reshaping of the immune environment triggered by CAR T cell administration, though the quality and nature of this remodeling varied distinctly between patients who responded favorably and those who did not.

Responders demonstrated marked activation of NK cells, a class of innate lymphocytes with potent cytotoxic functions capable of swiftly targeting and killing abnormal or stressed cells, including tumor cells. This NK cell activation correlated with greater tumor shrinkage and extended overall survival, underscoring the critical role of harnessing innate immunity alongside adaptive CAR T cell targeting in combating GBM. The data suggest that an orchestrated interplay between engineered CAR T cells and the endogenous immune compartment amplifies antitumor effects.

Conversely, non-responders exhibited increased proportions of activated Tregs and immunosuppressive myeloid lineage cells within their CSF. These cells contribute to immune tolerance by dampening effector immune responses, thereby enabling tumor cells to evade immune-mediated destruction. Importantly, a higher baseline abundance of these immunosuppressive populations was predictive of poorer therapeutic outcomes, highlighting these cells as potential barriers to CAR T efficacy.

This study elucidates how the dynamic immune microenvironment within the central nervous system is a decisive factor shaping the success or failure of CAR T therapy in recurrent GBM. By capturing this immune modulation longitudinally through CSF sampling, the research offers a real-time window into the evolving battle between tumor and immune system—a feat rarely achievable in solid tumors due to the invasive nature of brain sampling.

Looking ahead, these insights pave the way for rational design of next-generation CAR T therapies optimized to overcome the suppressive tumor milieu. Strategies may include preconditioning regimens that selectively deplete Tregs or inhibitory myeloid cells before CAR T infusion, or genetically engineering CAR T cells “armed” with molecular tools to neutralize immunosuppressive signals locally within the brain. Such combinatorial approaches could potentiate better tumor control and durable remissions.

Furthermore, the deployment of CSF-based liquid biopsy techniques offers a transformative clinical tool for personalized monitoring. Tracking immune cell subsets and activation states could tailor therapeutic adjustments for individual patients, enabling precision immunotherapy guided by the tumor’s evolving immune landscape rather than static tissue biopsies.

Pending expanded evaluation in ongoing Phase I clinical trials (ClinicalTrials.gov identifiers: NCT07209241 and NCT05168423), this dual-target CAR T cell platform heralds a promising frontier in tackling GBM. It exemplifies how integrating advanced cellular therapies with in-depth immune profiling can elucidate resistance mechanisms and unlock pathways for clinical improvement in cancers once deemed intractable.

In sum, this research not only advances scientific understanding of CAR T mechanisms in solid malignancies but also offers hope for enhanced therapeutic strategies against one of the deadliest brain cancers. Elevating the endogenous immune compartment, particularly innate effectors like NK cells, represents a pivotal axis for augmenting CAR T cell efficacy and ultimately improving survival for patients battling recurrent glioblastoma.

Subject of Research: People

Article Title: The critical role of endogenous immune compartment after CAR T cell therapy in recurrent GBM

News Publication Date: Not specified

Web References:

• https://www.pennmedicine.org/news/dual-target-car-t-cell-therapy-slows-growth-of-aggressive-brain-cancer
• https://clinicalresearch.pennmedicine.org/us/en/listing/9046/upcc-10325-phase-ib-NCT07209241-696/
• https://clinicalresearch.pennmedicine.org/us/en/listing/7338/upcc-16321-phase-1-NCT05168423-696/

References: Published in Cell

Keywords: CAR T cell therapy, glioblastoma, recurrent GBM, cerebrospinal fluid, intracerebroventricular infusion, immune microenvironment, natural killer cells, regulatory T cells, immunosuppression, single-cell RNA sequencing, immunotherapy, personalized medicine

Chimeric antigen receptor T cell therapy, or CAR-T, fundamentally rewires a patient’s immune system to better target and destroy cancer cells. By engineering T cells to express synthetic receptors specific to antigens found on malignant B cells, these treatments harness and enhance the immune response against cancer. However, the specificity against B cell lineage presents a double-edged sword; while it effectively eradicates malignant cells, it also profoundly depletes normal B cells, the pivotal architects of humoral immunity.

Humoral immunity, broadly defined by the production of antibodies from B cells, is the body’s frontline defense against many pathogens. The depletion of B cells, induced by B cell-lineage targeted CAR-T therapies, profoundly disrupts this defense system. The study by Ozog et al. meticulously dissects how this targeted depletion alters the trajectory of antibody production and the functional capacity of residual immune components. Intriguingly, the research highlights that patients experience long-lasting deficits in antibody generation, an outcome with significant clinical implications.

Among the most pressing concerns raised is the diminished antibody response to vaccinations in patients who have undergone B cell-lineage CAR-T therapy. Vaccines rely on a functional humoral component to generate protective immunity; without adequate B cell populations, the efficacy of vaccines is severely compromised. The study’s data show a marked reduction in vaccine-induced seroconversion, indicating that recently treated patients may remain susceptible to infections despite standard immunization protocols.

What further complicates this picture is the heterogeneous nature of immune recovery following CAR-T therapy. The investigation reveals variability in the kinetics of B cell reconstitution among patients, influenced by factors including the CAR-T cell construct used, the disease treated, and individual patient immunologic baseline status. This variability signifies that personalized post-therapy monitoring of immune function is imperative to guide vaccination timing and protective measures.

In exploring the mechanistic underpinnings of these phenomena, the researchers employed advanced immunophenotyping and serological assays. By tracking B cell subsets and antibody titers longitudinally, they demonstrated a persistent absence of certain naive and memory B cell populations post-therapy. This depletion disrupts not only immediate antibody generation but also impairs the establishment of immunologic memory, critical for durable vaccine responses.

Additionally, the study probes the interplay between CAR-T cells and the broader immune microenvironment. The engineered T cells, while selectively cytotoxic, might also exert off-target effects or induce bystander immune modulation. The authors observe alterations in cytokine profiles and helper T cell function, suggesting a more complex immunosuppressive milieu that extends beyond mere B cell elimination.

Considering these findings, the clinical ramifications are profound. Patients undergoing B cell-targeted CAR-T therapy represent a vulnerable population with impaired adaptive immunity. Current vaccination strategies might require adaptation, either through additional booster doses, modified vaccine formulations, or alternative prophylactic interventions such as monoclonal antibody therapies. Further research is needed to define optimal vaccination schedules tailored to the unique immune landscapes of these individuals.

Moreover, the insights from this study provide a cautionary tale regarding the use of B cell-depleting immunotherapies during ongoing viral pandemics or in settings where emerging infectious diseases threaten vulnerable populations. Without robust humoral immunity, the risk of severe infections and poor vaccine responsiveness could escalate, complicating patient care and public health strategies.

The authors advocate for integrated management approaches combining immunologic monitoring with therapeutic interventions designed to support immune recovery. Strategies under consideration include administering immune stimulants, adoptive transfer of B cells, or even developing CAR-T constructs that spare non-malignant B cell populations, thereby preserving essential humoral immune functions.

From a scientific perspective, this study opens new avenues for deeper exploration into the balance between targeted cancer therapy and maintaining immune homeostasis. It challenges the community to innovate beyond cancer cell eradication towards therapies that harmonize tumor control with immune preservation. The meticulous characterization of immune dysfunction after CAR-T therapy will undoubtedly inform next-generation immunotherapies that are both effective and less immunocompromising.

In conclusion, the work by Ozog et al. represents a pivotal advancement in our understanding of how B cell-lineage targeted CAR-T cell therapy reshapes the immune landscape. Their comprehensive evaluation of humoral immunity and vaccine-induced antibody responses provides crucial insight into the vulnerabilities faced by patients after such treatments. This knowledge equips clinicians and researchers with the information necessary to refine immunotherapeutic protocols and vaccination strategies, ensuring safer and more effective management of patients battling malignancies with these cutting-edge therapies.

As CAR-T therapy continues its transformative impact across oncology, appreciating the full scope of its immunologic consequences is essential. This study reinforces that optimizing cancer treatment outcomes must be coupled with safeguarding immune competence, particularly in a world where vaccine protection remains vital. Addressing these challenges will be paramount as the field moves toward personalized immuno-oncology and comprehensive patient care.

Subject of Research:
Influence of B cell-lineage targeted CAR-T cell therapy on humoral immunity and vaccine-induced antibody response.

Article Title:
Influence of B cell-lineage targeted CAR-T cell therapy on humoral immunity and vaccine-induced antibody response.

Article References:
Ozog, S., Krantz, E.M., Tindbaek, K. et al. Influence of B cell-lineage targeted CAR-T cell therapy on humoral immunity and vaccine-induced antibody response. Nat Commun (2026). https://doi.org/10.1038/s41467-026-71473-1

Image Credits: AI Generated

Chimeric antigen receptors function by equipping T cells with synthetic receptors that recognize tumor-specific antigens. The receptor features an extracellular antigen-binding domain, typically derived from antibody fragments, enabling exquisite specificity to cancer cell surface markers. Detection of the target antigen triggers intracellular signaling cascades initiated by the CD3-ζ domain combined with co-stimulatory components such as CD28, prompting cytotoxic T cell activation and elimination of malignant cells. While potent, this design is irreversible once activated, which can lead to unrestrained T cell activity, causing on-target, off-tumor toxicities and cytokine release syndromes.

The novel technology developed by Irving, Giordano Attianese, and colleagues enhances control over CAR-T cells via a ‘drug-regulated off-switch protein-protein interaction CAR’ (DROP-CAR) that modulates receptor integrity at the cell surface. This system does not rely on degrading CAR components or inducing CAR-T cell death, as previous off-switch designs did. Instead, it harnesses a finely engineered protein interface consisting entirely of human-derived elements, thus minimizing immunogenicity. The extracellular domain includes a computationally designed human protein, dubbed dmLD3, which binds BCL-2 with exceptional affinity. The CAR’s antigen-binding moiety is appended with a complementary BCL-2 fragment. In the assembled complex, the dmLD3 and BCL-2 components maintain CAR integrity through spontaneous protein-protein interactions.

Venetoclax, an FDA-approved cancer drug known for its high-affinity binding to BCL-2, serves as the molecular remote control in this system. Administration of venetoclax competitively disrupts the dmLD3-BCL-2 interaction, causing the extracellular CAR architecture to dissociate and the receptor to disassemble, effectively silencing the CAR-T cell’s tumor-targeting function. Crucially, the CAR receptors then swiftly reassemble upon venetoclax withdrawal, restoring cytotoxic activity. This reversible mechanism allows precise temporal modulation of CAR-T cell functionality without triggering apoptosis or cell removal, preserving the therapeutic cell population across treatment cycles.

From a mechanistic perspective, this innovation exploits a novel strategy whereby the critical ligand-binding interface of the CAR is placed under direct drug inducible control on the cell surface, which represents a significant departure from intracellular control systems that target signaling components. This extracellular targeting permits instantaneous and direct regulation of tumor cell engagement, thereby avoiding downstream signaling perturbations that could have off-target effects or induce premature T cell exhaustion. The integration of entirely human protein constituents promises improved biocompatibility and clinical translatability.

One of the challenges that continuous CAR-T cell activity faces is antigen-driven exhaustion, a phenomenon whereby persistent stimulation in the immunosuppressive tumor microenvironment leads to a dysfunctional T cell state, marked by epigenetic and transcriptomic remodeling that curb effector functions. The DROP-CAR design provides a potential solution by enabling treatment protocols in which CAR-T cells can be transiently ‘paused,’ allowing them to rest and recover function before reactivation. Such temporal control could extend the durability and efficacy of CAR-T therapies against solid tumors, which often exhibit highly suppressive milieus.

The strategic use of venetoclax as both a therapeutic agent and an off-switch control element is ingenious, leveraging its established safety profile and clinical experience. Venetoclax’s known pharmacokinetics and dosage guidelines streamline potential regulatory hurdles, facilitating rapid translation from preclinical models to human trials. Moreover, unlike previous CAR modulation approaches that used exogenous small molecules or induced degradation pathways, this system’s non-immunosuppressive drug does not compromise host immunity, maintaining a favorable toxicity profile.

Preclinical validation in murine cancer models affirmed that DROP-CAR T cells retain robust antitumor efficacy when active and can be effectively switched off and back on with venetoclax dosing cycles. This on-demand control mitigates risks associated with systemic cytokine storms and off-target cytotoxicity without sacrificing anti-tumor potency. The researchers emphasize that this technology could democratize CAR-T therapy by broadening its applicability beyond hematologic malignancies to solid tumors and enhancing the safety margin of treatments.

This pioneering work signifies a conceptual leap in synthetic immunology by applying computational protein design to engineer high-affinity modulatable interfaces, integrating them into living cell therapies. The reversible ‘off-switch’ paradigm parallels the sophistication of electronic devices in continuously fine-tuning outputs to meet real-time physiological demands, reflecting a new frontier in precision immunotherapy. By empowering clinicians with this level of control, it may soon become possible to customize CAR-T regimens on a patient-specific basis, dynamically adjusting therapeutic intensity in response to individual tumor burden and immune status.

As the field of engineered cellular therapies continues to mature, such controllable CAR systems represent a paradigm shift that addresses some of the fundamental limitations restraining the broader success of CAR-T cells against complex, heterogeneous solid tumors. The ability to govern CAR function externally, without sacrificing cell viability or inducing immunosuppression, could transform the clinical management of cancer, improving both efficacy and safety. The work from Ludwig Lausanne and EPFL exemplifies translational excellence, wherein molecular engineering, drug repurposing, and immunobiology converge to realize next-generation cancer treatments.

Overall, this study provides a robust platform for future clinical investigations, with the potential to modulate CAR-T cell activity precisely, reduce toxicities, extend therapeutic windows, and ultimately improve patient outcomes in oncology. Given the serious unmet needs in solid tumor immunotherapy and the well-documented limitations of current CAR-T technologies, the DROP-CAR approach marks a substantial advancement toward safer and more adaptable cellular therapies.

Subject of Research:
Cancer Immunotherapy, CAR-T Cell Engineering, Protein-Protein Interaction Modulation

Article Title:
Remote-Controlled OFF-Switch CAR-T Cells Enable Precise, Reversible Modulation of Antitumor Activity with Venetoclax

News Publication Date:
February 19, 2026

Web References:
https://www.nature.com/articles/s41589-026-02152-x

Image Credits:
Ludwig Cancer Research

Keywords:
Health and medicine, Cancer, Immunology, Immunotherapy

As researchers delve deeper into the intricacies of immune responses, a prevalent area of investigation has emerged: the mechanisms that differentiate between therapeutic responders and non-responders. Among the various factors influencing the effectiveness of immunotherapy, T cell exhaustion has garnered increased attention. Characterized by a marked decline in T cell effector functions and proliferative capacity, exhaustion poses a considerable obstacle to successful cancer treatment. Understanding the nature and contributing factors of T cell exhaustion is crucial for the continued improvement of immunotherapies.

The mechanisms underlying T cell exhaustion are multifaceted, involving both transcriptional and epigenetic regulations. Researchers have identified a range of gene regulatory networks that govern T cell function, activation, and differentiation. These pathways often become disrupted in the tumor microenvironment, leading to a state of dysfunction that limits the ability of T cells to mount an effective immune response. The intricacies of these networks are now under rigorous investigation, as scientists work to elucidate their roles in influencing the fate of T cells within cancers.

Notably, the relationship between T cell exhaustion and the immunosuppressive tumor microenvironment has been a focal point for researchers. Various cytokines, metabolic alterations, and cell-cell interactions within this environment can sustain T cell exhaustion. For example, tumors often secrete factors that drive immune evasion, fostering a milieu that inhibits T cell activation and function. Additionally, the metabolic demands placed on T cells by the tumor’s aggressive growth patterns further exacerbate exhaustion, leading to diminished therapeutic efficacy.

Through their work, scientists are gradually uncovering the epigenetic modifications that contribute to T cell exhaustion. These modifications, which alter chromatin structure and control gene expression without changing the underlying DNA sequence, can be crucial in determining the fate of T cells. For instance, studies have demonstrated that alterations in DNA methylation and histone modification patterns can profoundly affect T cell functionality, thereby influencing the overall immune response against tumors.

Furthermore, it is now recognized that the state of T cell exhaustion is not a uniform condition, but rather a heterogeneous and dynamic process. Different T cell subsets exhibit varying levels of susceptibility to exhaustion, which in turn influences their ability to respond to immunotherapeutic interventions. Understanding the specific gene regulatory programs that operate within these subsets provides critical insights into how to tailor immunotherapy approaches to better address cancer’s challenges.

In light of these developments, there is a growing consensus among researchers that innovative strategies must be developed to enhance T cell activity and combat exhaustion. Next-generation approaches could focus on rewiring the transcriptional and epigenetic patterns associated with T cell dysfunction. This could involve the application of novel small molecules or biologics aimed at reversing epigenetic modifications, thereby restoring T cell efficacy and reinvigorating the immune response against tumors.

Additionally, combination therapies that leverage multi-faceted treatment paradigms may hold the key to overcoming T cell exhaustion. By integrating conventional treatments such as chemotherapy or targeted therapies with immunotherapies, researchers aim to create a synergistic effect that not only enhances the efficacy of treatment but also mitigates the conditions that lead to T cell exhaustion.

Collaborative efforts across disciplines will also be essential for advancing our understanding of T cell exhaustion in the context of different cancer types. By integrating genomics, proteomics, and advanced imaging techniques, scientists can gain a more holistic view of the interactions at play within the tumor microenvironment. This integrative approach can lead to the identification of novel biomarkers predictive of response to immunotherapy, paving the way for more personalized treatment strategies tailored to individual patients.

The journey to unlock the full potential of T cell-based immunotherapy is undoubtedly complex, yet the quest to understand and overcome T cell exhaustion offers immense promise. As research continues to evolve, the hope is that a greater number of patients will be able to benefit from these therapeutic innovations, leading to enhanced survival rates and improved quality of life for those diagnosed with cancer.

Ultimately, the ongoing exploration of T cell exhaustion embodies the intricacies of cancer biology, revealing critical insights that can inform and shape future therapeutic strategies. With continued innovation and collaboration, the fight against cancer stands to gain tremendously from the advancements in understanding T cell functionality, ultimately fostering a new era of effective and durable immune-based therapies.

Subject of Research: T cell exhaustion in cancer.

Article Title: Epigenetic regulation of T cell exhaustion in cancer.

Article References:

Kang, T.G., Johnson, J.T., Zebley, C.C. et al. Epigenetic regulation of T cell exhaustion in cancer.
Nat Rev Cancer 26, 46–61 (2026). https://doi.org/10.1038/s41568-025-00883-y

Image Credits: AI Generated

DOI: https://doi.org/10.1038/s41568-025-00883-y

Keywords: T cell immunotherapy, cancer treatment, T cell exhaustion, immune checkpoint blockade, chimeric antigen receptor T cells, epigenetic regulation, transcriptional mechanisms, tumor microenvironment, combination therapies, personalized medicine.