Targeting γδ T cells for immunotherapies against colorectal cancer

The advancement of immunotherapy faces significant challenges, including extending its benefits to a growing number of patients and enhancing its efficacy across different tumor types. In this context, γδ T cells emerge as particularly promising candidates owing to their distinctive biological features such as MHC-independent activation, potent cytotoxicity, and capacity to bridge innate and adaptive immunity. Recently, advanced single-cell techniques have allowed detailed γδ T cell characterization in the tumor microenvironment (TME) and have emphasized their heterogeneity, mechanisms of activation, and response to immune checkpoint blockade (ICB). This review provides a comprehensive summary of recent advances in understanding γδ T cells in colorectal cancer (CRC), with a particular emphasis on their prognostic and therapeutic relevance in both primary tumors and metastatic disease.