Lymphoma response to chimeric antigen receptor T cell therapy is driven by endogenous tumor-reactive CD8⁺ T cells

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1. Very close Review Not relevant

   CAR T cell cancer immunotherapy: who does the job?

   D. Harrer, Markus Barden, H. Abken · 2026 · Frontiers in Immunology · Not summarized yet

   “CAR T cell cancer immunotherapy: who does the job?” reviews how endogenous adaptive and innate immune cells contribute to CAR-T outcomes.

   Abstract

   Chimeric antigen receptor (CAR) T cells are capable to eliminate cancer cells in the treatment of hematologic malignancies, yet the efficacy is frequently inconsistent and limited by cancer cell resistance and antigen-loss resulting in early tumor relapses. While CAR T cells are deemed to be the primary effectors in controlling the tumor, maturing evidence indicates that therapeutic outcomes are shaped by a broader immune cell network involving both the endogenous adaptive and innate immunity. In this review, we reframe CAR T cell therapy as the induction of a multi-system immune response rather than a uni-directional cytotoxic cell-autonomous intervention. We discuss the respective contribu…

2. Very close Same question Not relevant

   CD8 T-cell exhaustion linked with CAR T-cell failure can be mitigated by a non-alpha IL2 receptor agonist.

   Kotaro Arita, En-Yu Dai, Xu-Bin Li et al. · 2026 · Blood · Not summarized yet

   “CD8 T-cell exhaustion linked with CAR T-cell failure” studies immune mechanisms of CART19 failure in relapsed or refractory large B-cell lymphoma, focusing on CAR-T cell exhaustion.

   Abstract

   Chimeric antigen receptor T-cell (CART19) therapy represents a breakthrough for relapsed or refractory large B-cell lymphoma (rrLBCL). However, suboptimal CART19 activity can lead to therapeutic failure and dismal outcomes. Through single cell RNA-sequencing of tumors at the time of progression from CART19, we show that a subset of tumor contain clonally expanded and proliferating populations of CART19 cells that acquire transcriptional features of dysfunction, suggestive of ongoing tumor cell engagement and chronic stimulation. Using an in vitro system to model this process, we show that iterative rechallenge of CART19 cells with target cells drives failure of tumor control associated with …

3. Very close Another approach to the problem Not relevant

   Model-based integration of chimeric antigen receptor T-cell kinetics and tumor features to predict therapeutic outcomes in patients with B-cell malignancies

   Jonas Schadt, M. Rohnert, Paul Matthiensen et al. · 2026 · Frontiers in Immunology · Not summarized yet

   “Model-based integration” predicts outcomes in B-cell malignancies by combining CAR-T kinetics and tumor features in a mechanistic model.

   Abstract

   Introduction Chimeric antigen receptor (CAR) T-cell therapy is a standard treatment for several hematological malignancies, yet patient-specific responses and toxicities remain hard to predict. Although multiple covariates and risk scores exist, their prognostic accuracy remains limited. Methods We prospectively measured CAR T-cell kinetics in peripheral blood of 92 patients with B-cell malignancies using multicolor flow cytometry. To explore underlying mechanisms, we developed a mechanistic model of CAR T-cell and tumor cell interactions. Results We captured four phases of CAR T-cell kinetics in peripheral blood: distribution, expansion, contraction, and persistence. Patients with weak expa…

4. Very close Review Not relevant

   Clinical and Biological Correlates of Resistance and Relapse After CD19-Directed CAR T-Cell Therapy in Large B-Cell Lymphoma: A Structured Narrative Review

   Jean Silva de Souza Resende, I. S. Giner, Maria Gabriela Custodio de Figueiredo et al. · 2026 · Cancers · Not summarized yet

   “Clinical and Biological Correlates” reviews clinical and biological factors associated with resistance and relapse after CD19-directed CAR-T therapy in large B-cell lymphoma.

   Abstract

   Simple Summary CD19-directed chimeric antigen receptor (CAR) T-cell therapy has transformed the treatment of large B-cell lymphoma (LBCL), but many patients either do not respond or subsequently relapse. This structured narrative review examines clinical outcomes and biological factors associated with resistance and relapse. Across 14 studies, treatment failure could not be attributed to loss of CD19 alone, although incomplete assessment of CD19 at relapse limits this interpretation. Tumor-intrinsic programs, impaired CAR T-cell fitness and persistence, systemic inflammation, and an immunosuppressive tumor microenvironment also contributed, although differences in study design and incomplete…

5. Very close Broader context Not relevant

   T-cell lymphoma following chimeric antigen receptor-T therapy: a cause for concern?

   Federico Stella, J. Fraietta, S. Schuster et al. · 2026 · Haematologica · Not summarized yet

   “T-cell lymphoma following chimeric antigen receptor-T therapy” reviews rare secondary T-cell lymphomas as a long-term safety concern after CAR-T treatment.

   Abstract

   Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of relapsed or refractory B-cell malignancies and multiple myeloma, with tens of thousands of patients treated worldwide. As survival improves, long-term safety has come into focus, and rare reports of T-cell lymphomas occurring after CAR T-cell infusion have prompted regulatory scrutiny and heightened clinical attention. Drawing on pivotal trials, real-world registries, meta-analyses, pharmacovigilance data, and detailed molecular case reports, we review the incidence, biological plausibility, and clinical relevance of lymphomas arising after CAR T-cell therapy. Registry data and large institutional series consi…

6. Very close Review Not relevant

   Relapse and progression after CAR-T cell therapy in large B-cell lymphoma: Patterns, mechanisms, and salvage strategies.

   Ling-Zhi Wang, Qing Li, Xiao-Jian Zhu · 2026 · Cancer Treatment and Research Communications · Not summarized yet

   “Relapse and progression after CAR-T cell therapy” reviews relapse patterns, mechanisms, risk factors, and salvage strategies in large B-cell lymphoma.

   Abstract

   Chimeric antigen receptor (CAR)-T cell therapy has transformed the treatment landscape for large B-cell lymphoma (LBCL), particularly in the relapsed or refractory. However, relapse after CAR-T cell therapy remains a major barrier to durable remission and long-term survival because post-CAR-T relapse is biologically and clinically heterogeneous and lacks standardized management strategies. In this narrative review, we provide a clinically oriented synthesis of the current evidence on relapse or progression after CAR-T cell therapy in LBCL, focusing on relapse patterns, underlying biological mechanisms, risk factors, and evolving salvage strategies. Evidence from other B-cell lymphoma subtype…

7. Very close Broader context Not relevant

   Targeting Peripheral T-Cell Lymphomas with Chimeric Antigen Receptor Therapy: Mechanistic Challenges, Clinical Landscape and Future Engineering Perspectives

   R. Irimia, P. Piccaluga · 2026 · Cancers · Not summarized yet

   “Targeting Peripheral T-Cell Lymphomas” reviews CAR therapy challenges in T-cell lymphoma, a different cancer from the B-cell lymphoma studied here.

   Abstract

   Simple Summary Peripheral T-cell lymphomas are aggressive forms of cancers caused by mature T lymphocytes. These cancers respond poorly to standard chemotherapy, leaving a pressing need for new treatments. Chimeric antigen receptor (CAR) cell therapy, which reprograms immune cells to recognize and kill tumor cells, has transformed the treatment of B-cell cancers, but its use against T-cell tumors has been held back by problems unique to T-cell lineage: the engineered cells tend to attack one another, healthy T-cells can be destroyed alongside the cancer, and tumor cells can contaminate the therapeutic product. This review summarizes how newer engineering strategies address these obstacles, e…

8. Very close Broader context Not relevant

   Targeting the tumor, harboring the host: IL-7 receptor-targeted CARs to treat T-ALL

   V. Kuznetsova, Rishi K. Kothuru, P. Adusumilli et al. · 2026 · Molecular therapy. Oncology · Not summarized yet

   “Targeting the tumor, harboring the host” discusses IL-7 receptor-targeted CARs for T-ALL and the fratricide problem caused by shared antigens.

   Abstract

   Chimeric antigen receptor (CAR) T cell therapy has fundamentally transformed clinical outcomes in B cell malignancies; however, the success story of CAR T cells has not yet extended to T cell acute lymphoblastic leukemia (T-ALL). A primary issue lies in the fundamental biology of the disease; most target antigens are shared be-tween malignant T-ALL blasts and healthy T lymphocytes, including the CAR T cell product itself. This overlap triggers fratricide, a unique on-target, off-tumor toxicity in which CAR T cells recognize and destroy each other as well as bystander normal T cells. This self-destruction compromises the manufacturing yield, impairs in vivo persistence, and introduces the ris…