Cancer immunotherapy has been revolutionized by targeting specific immune subsets within the tumor microenvironment, where T cells play a pivotal role. Gene-engineered T cell strategies and immune checkpoint blockade (ICB) therapies have emerged as powerful approaches to reinvigorate tumor-infiltrating T cells, demonstrating considerable promise in clinical outcomes. However, challenges persist, particularly the limited in vivo persistence of adoptively transferred T cells and the variable patient response rates to ICB therapy. Key barriers include T cell exhaustion and the immunosuppressive milieu of the tumor microenvironment. Consequently, a deep understanding of functional modulation of these immune subsets is urgently needed to enhance the efficacy and safety of various T cell therapies, such as Tumor-infiltrating T lymphocytes (TIL-T), T cell receptor-engineered T cells (TCR-T), and Chimeric antigen receptor T cells (CAR-T).

This Research Topic aims to explore and identify crucial targets and pathways for overcoming immune dysregulation in the tumor microenvironment. We seek to advance our understanding of these complexities by discussing innovative techniques that could augment T cell antitumor functionality. Contributions that unveil novel approaches or refine existing methods to boost the therapeutic potential of T cells in cancer treatment are particularly encouraged.

To gather further insights into the underlying mechanisms and optimize therapeutic strategies in cancer immunotherapy, this Research Topic is focused on exploring both basic and clinical advancements. We invite submissions that are dealing with:
o New immune subsets mediating antitumor immunity
o Checkpoints that limit the polarization and expansion of antitumor immune subsets
o Responses of T cell subsets to checkpoint blockade immunotherapy
o The role of stem-like CD8+ T cells within the tumor microenvironment
o Pathways and mechanisms promoting the expansion of antitumor stem-like CD8+ T cells
o Enhancing the efficiency and persistence of TCR-T and CAR-T cell therapies
o Influence of tumor-associated macrophages on T cell function

These themes will prove critical in pushing the frontier of T cell-based therapies and improving patient outcomes in the face of cancer.

Manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this topic.

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Frontiers in Immunology

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