Single-cell RNA sequencing of human double-negative T cells reveals a favorable cellular signature for cancer therapy

Journal for ImmunoTherapy of Cancer, Год журнала: 2025, Номер 13(4), С. e010684 - e010684

Опубликована: Апрель 1, 2025

Background Allogeneic double-negative T-cell (DNT) therapy has emerged as a novel, off-the-shelf cellular treatment with clinical feasibility, safety, and promising efficacy against leukemia. However, the biology of DNTs is less well characterized, how DNT distinguishes from conventional γδ remains unclear. Collectively, this hinders our ability to bolster functionalities in cancer therapy. Here, we performed single-cell RNA sequencing vitro vivo functional analysis on DNTs. As significant proportion express Vγ9Vδ2 (Vδ2) TCR chain, compared donor-matched Vδ2 T cells expanded zoledronic acid. Methods Healthy donor-derived allogeneic were ex vivo. Single-cell was both products identify transcriptional landscape inferred interactions within DNTs, followed by comparisons cells. Unique subsets found only depleted their contributions overall acute myeloid The anti-leukemic activity persistence T-cells explored using flow cytometry-based cytotoxicity assays, memory phenotyping, xenograft models. Results Despite shared expression between products, identified unique compositions that contribute distinct communication patterns relative cells, including higher genes chimeric antigen receptor persist patients durable cancer-remission. – exhibited strong characteristics, presence promoted cytotoxic capabilities + repeated stimulation assays. This genetic signature diverse composition resulted better expansion, prolonged persistence, superior Conclusions These results highlight transcriptional, cellular, profile human support continued investigation data also provide reference gene may help improve other types adoptive therapies.

Язык: Английский

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Advances in CAR-T-cell therapy in T-cell malignancies

Journal of Hematology & Oncology, Год журнала: 2024, Номер 17(1)

Опубликована: Июнь 24, 2024

Abstract Significant advances have been made in chimeric antigen receptor T (CAR-T)-cell therapy for the treatment of recurrent or refractory B-cell hematologic malignancies. However, CAR-T-cell has not yet achieved comparable success management aggressive T-cell This article reviews challenges treating malignancies and summarizes progress preclinical clinical studies this area. We present an analysis trials therapies grouped by target classification. Moreover, review focuses on major encountered therapies, including nonspecific killing due to sharing contamination with cell products during preparation. discusses strategies overcome these challenges, presenting novel therapeutic approaches that could enhance efficacy applicability These ideas provide important information future promote further development application field.

Язык: Английский

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T-cell Redirecting Therapies in Haematological malignancies: Current Developments and Novel Strategies for Improved Targeting

Molecular Therapy, Год журнала: 2024, Номер 32(9), С. 2856 - 2891

Опубликована: Авг. 5, 2024

T cell-redirecting therapies (TCRTs), such as chimeric antigen receptor (CAR) or cell (TCR) cells and engagers, have emerged a highly effective treatment modality, particularly in the B plasma cell-malignancy setting. However, many patients fail to achieve deep durable responses; while lack of truly unique tumor antigens, concurrent on-target/off-tumor toxicities, hindered development TCRTs for other cancers. In this review, we discuss recent developments TCRT targets hematological malignancies, well novel targeting strategies that aim address these, other, challenges.

Язык: Английский

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Potential alternatives to αβ-T cells to prevent graft-versus-host disease (GvHD) in allogeneic chimeric antigen receptor (CAR)-based cancer immunotherapy: A comprehensive review

Pathology - Research and Practice, Год журнала: 2024, Номер 262, С. 155518 - 155518

Опубликована: Авг. 10, 2024

Язык: Английский

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Modulation of double-negative T cells by Huang-Lian-Jie-Du Decoction attenuates neuroinflammation in ischemic stroke: insights from single-cell transcriptomics

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Фев. 13, 2025

Introduction Ischemic stroke (IS) represents a significant global health challenge, characterized by elevated morbidity and mortality rates, largely driven inflammatory responses. Double-negative T cells (DNTs), distinct subset of lacking both CD4 CD8 markers, have been implicated in the pathogenesis IS, exhibiting potentially dual roles. However, precise functional contributions DNTs this context remain poorly understood. Methods In study, we investigated role during acute phase IS assessed influence Huang-Lian-Jie-Du Decoction (HLJD), traditional Chinese medicinal formula, on these cells. Using single-cell transcriptomics, identified two subtypes DNTs: an activated, cytotoxic phenotype (Kill+) resting, immunosuppressive (Kill-). Results Our findings indicate that HLJD treatment modulates balance between DNT subtypes, specifically reducing proportion while promoting increase DNTs. This shift was associated with reduction immune cell infiltration inflammation within brain tissue, mitigating neuronal damage. Discussion These results suggest exerts neuroprotective effects modulating activity distribution cells, offering valuable insights into therapeutic potential medicine for IS. Further studies are required to elucidate mechanisms underlying DNT-mediated responses explore broader applications other neuroinflammatory conditions.

Язык: Английский

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Clinical Progress of CAR-T Cell Therapy for Refractory/Relapsed Acute T Lymphoblastic Leukemia

Advances in Clinical Medicine, Год журнала: 2025, Номер 15(03), С. 676 - 685

Опубликована: Янв. 1, 2025

Язык: Английский

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The mouse resource at National Resource Center for Mutant Mice of China

Mammalian Genome, Год журнала: 2025, Номер unknown

Опубликована: Март 27, 2025

Язык: Английский

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Allogeneic double-negative T-cell therapy for acute myeloid leukemia

Current Opinion in Pharmacology, Год журнала: 2025, Номер unknown, С. 102537 - 102537

Опубликована: Май 1, 2025

Язык: Английский

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Double negative T-cells in acute lymphoblastic leukemia: a pilot study in pediatric patients

Medicine and ecology, Год журнала: 2025, Номер 1, С. 105 - 115

Опубликована: Май 16, 2025

Objective . Double negative T cells are involved in various neoplastic processes including hematologic malignancies such as acute lymphoblastic leukemia. These unconventional lymphocytes express neither CD4 nor CD8 and play a role immune modulation cancer, particularly the bone marrow microenvironment. However, their specific involvement leukemia other leukemias, especially pediatric patients, remains poorly understood. The present pilot study aims to characterize double T-cells children with compare them healthy controls. Materials methods. A prospective, cross-sectional of 20 diagnosed 9 healthy, ageand sex-matched control participants was performed. Flow cytometry used evaluate lymphocyte subpopulations, T-cells. Results Discussion total number significantly increased patients compared In particular, αβ+DNT were markedly both percentage absolute values. At same time, γδ+DNT decreased proportion CD3+ lymphocytes. Conclusions elevated leukemia, suggesting possible response this increase may reflect broader dysregulation rather than being Further studies required clarify explore therapeutic potential.

Язык: Английский

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Broadening the horizon: potential applications of CAR-T cells beyond current indications

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Ноя. 27, 2023

Engineering immune cells to treat hematological malignancies has been a major focus of research since the first resounding successes CAR-T-cell therapies in B-ALL. Several diseases can now be treated highly therapy-refractory or relapsed conditions. Currently, number CD19- BCMA-specific are approved for acute lymphoblastic leukemia (ALL), diffuse large B-cell lymphoma (DLBCL), mantle cell (MCL), multiple myeloma (MM), and follicular (FL). The implementation these significantly improved patient outcome survival even cases with previously very poor prognosis. In this comprehensive review, we present current state research, recent innovations, applications therapy selected group hematologic malignancies. We on B- T-cell malignancies, including entities cutaneous peripheral (T-ALL, PTCL, CTCL), myeloid (AML), chronic (CML), lymphocytic (CLL), classical Hodgkin-Lymphoma (HL), Burkitt-Lymphoma (BL), hairy (HCL), Waldenström’s macroglobulinemia (WM). While heterogenous, highlight several similarly used approaches (combination established therapeutics, target depletion healthy cells), targets (CD30, CD38, TRBC1/2), unique features that require individualized approaches. Furthermore, limitations individual such as immunocompromising tumor microenvironment (TME), risk on-target-off-tumor effects, differences occurrence adverse events. Finally, an outlook into novel innovations engineering like use artificial intelligence future role CAR-T regimens everyday clinical practice.

Язык: Английский

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