Decoding the tumor immune landscape: emerging TIL subsets as prognostic biomarkers and therapeutic targets

Tumor -infiltrating lymphocytes (TILs) play a pivotal role in cancer immunity, with CD3 + T cells and CD8 + cytotoxic T cells historically regarded as key prognostic markers. Other TIL subsets are CD4 + T helper cells, regulatory T cells (Tregs), tissue-resident memory T cells (TRM cells), and non-traditional T cell populations like γδ T cells and innate-like T cells. These subsets have diverse roles which influence the disease duration and immunotherapy mechanism, from immune evasion to tumor suppression. TRM cells which are recognized by the expression of CD103 and CD69 are linked with better survival and enhance tumor management, while Tregs function mainly in the tumor microenvironment (TME). Additionally, γδ T cells have strong anti-cancer activity. Developments in single-cell sequencing and spatial transcriptomics have improved the understanding of TIL heterogeneity and their functional states, enhancing their prognostic and therapeutic significance. Understanding how different expanded TIL subgroups impact treatment response helps to recognize new biomarkers and therapeutic targets. This review investigates functions of TIL populations beyond the traditional markers like CD3 and CD8 across different cancers while concentrating on predictive outcomes in immunotherapy.