T cells are central players in cancer immunotherapy. Despite much concentrated effort on the study of tumor-infiltrating lymphocytes (TIL), such as T cells, a series of fundamental properties that include heterogeneity, clonal expansion, migration, and functional state transition remain elusive. Advances of single-cell sequencing have enabled the detailed characterization of immune cells in tumors and have vastly improved our understanding of less-defined cell subsets. Here, we discuss the current strategies for uncovering the heterogeneity of TILs, and how the deep transcriptome coupled with T-cell receptor analysis enhances the understanding of detailed properties of T-cell subsets. We further discuss the identification of novel T-cell markers with therapeutic or prognosis potentials, and highlight distinct T-cell properties among different cancer indications.
©2019 American Association for Cancer Research.