Phenotype molding of T cells in colorectal cancer by single‐cell analysis

The majority of patients with microsatellite stable (MSS) colorectal cancer (CRC) do not benefit from the immunotherapies directed at rescuing T‐cell functions. Therefore, complete understanding of T‐cell phenotypes and functional status in the CRC microenvironment is desirable. Here, we applied single‐cell mass cytometry to mold the T‐cell phenotype in 18 patients with MSS CRC for better understanding of CRC as a systemic disease and to search for tumor‐driven T‐cell profile changes. We show interpatient and intrapatient phenotypic diversity of T‐cell subsets. We revealed increased immunosuppressive/exhausted T‐cell phenotypes at tumor lesions. CD8+ CD28− immunosenescent T cells with impaired proliferation capacity dominate the T‐cell compartment. As per the transcriptome and quantitative real time‐PCR analysis, the accumulation of immunosuppressive cells is driven by the tumor microenvironment. T‐cell profiles are similar between patients at early and late stages, indicating that the immunosuppressive microenvironment is formulated early during CRC development. Mapping of T‐cell infiltration and understanding of the mechanisms underlying their regulation may provide valuable information to boost the immune response in patients with MSS CRC.