Harnessing T Cells and Emerging Strategies in Tumor Immunotherapy

T cells are central to cancer immunotherapy, with strategies ranging from immune checkpoint blockade and adoptive cell transfer to engineered therapies such as CAR-T and tumor-infiltrating lymphocytes (TILs). While αβ T cell-based approaches have achieved remarkable clinical success, their reliance on MHC-restricted antigen recognition can limit applicability in heterogeneous tumors. In this broader context, γδ T cells have emerged as a unique and promising effector arm of the immune system, bridging innate and adaptive immunity. Unlike conventional αβ T cells, γδ T cells recognize antigens in an MHC-unrestricted manner, enabling them to target a wide range of tumors without personalized neoantigen identification. Their intrinsic capacity for rapid cytokine secretion, direct cytotoxicity, and professional antigen-presenting cell functions positions them as attractive candidates for next-generation immunotherapy. However, despite their potential, challenges remain—including limited persistence in the tumor microenvironment, functional exhaustion, and the need for optimized expansion and engineering strategies. Recent advances in CAR engineering, bispecific antibodies, checkpoint blockade, and metabolic modulation are now being applied to both αβ and γδ T cell platforms. This Research Topic welcomes contributions that explore the full spectrum of T cell-based immunotherapies—with a special emphasis on, but not limited to, γδ T cells—across all cancer types.The goal of this Research Topic is to provide a comprehensive overview of current advances and future directions in T cell-based cancer immunotherapies, while highlighting emerging strategies centered on γδ T cells. We aim to gather cutting-edge original research, reviews, and perspectives addressing key bottlenecks in the field—including enhancing T cell expansion and persistence in vivo, overcoming immune suppression within the tumor microenvironment, and engineering T cells with CARs or other synthetic receptors. We are particularly interested in γδ T cell biology and therapeutic applications, but also welcome studies on αβ T cells, CAR-T, TILs, and combination approaches with standard-of-care treatments. By presenting both fundamental mechanistic studies and translational/clinical findings, this collection seeks to accelerate the development of novel T cell-based strategies and ultimately improve outcomes for cancer patients across diverse malignancies.Please note: Manuscripts consisting solely of bioinformatics, computational analysis, or predictions of public databases which are not accompanied by validation (independent clinical or patient cohort, or biological validation in vitro or in vivo, which are not based on public databases) are not suitable for publication in this journal. Topic editors: Mohammed Alnaggar, Yan Xu, Likai Tan, Jianlei Hao, Kok Fei (Jimmy) Chan, PhD Source: https://www.frontiersin.org/research-topics/80834/harnessing-t-cells-and-emerging-strategies-in-tumor-immunotherapy