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.