Di J, Liu M, Fan Y, et al. - Since most of the patients suffering from microsatellite stable (MSS) colorectal cancer (CRC) do not derive benefit from the immunotherapies aimed at rescuing T cell functions, so, it is desirable to acquire a full understanding of T cell phenotypes and functional status in the CRC microenvironment, researchers performed this study to gain a better understanding of CRC as a systemic disease as well as to investigate tumor-driven T cell profile alterations. For this purpose, they employed single-cell mass cytometry to mold the T cell phenotype in 18 patients with MSS CRC. The inter- and intrapatient phenotypic heterogeneity of T cell subsets was revealed. At tumor lesions, increased immunosuppressive/exhausted T cell phenotypes were identified. The tumor microenvironment was identified as the driver of the accumulation of immunosuppressive cells, as revealed in transcriptome and quantitative real time-PCR analysis. In patients at early vs late stages, a similarity in T cell profiles was observed. This suggests the formulation of an immunosuppressive microenvironment early during CRC development. In patients with MSS CRC, important information to boost the immune response may be obtained through the mapping of T cell infiltration and by knowing the mechanisms underlying their regulation.