Understanding tumor-infiltrating lymphocytes by single cell RNA sequencing.

The clinical success of immune checkpoint blockade provides great hope for curing cancers. However, the patient responses are not even. Precise understanding of tumor immunity is necessary to improving the current cancer immunotherapies and to developing new treatment options. Here we applied full-length single cell RNA-seq (scRNA-seq) to three cancer types and provide a comprehensive single T cell data resource for understanding various characteristics of tumor-infiltrating T cells. We also developed an analytical framework named as STARTRAC to quantitatively characterize the dynamic properties of various T cell subsets including tissue preference, clonal expansion, migration, and state transitions from the scRNA-seq snapshots of tumor immune microenvironments. Conserved and cancer type-specific T cell subsets and developmental patterns were revealed, and detailed molecular portrait of the tumor immunity-relevant T cell clusters were provided, shedding lights into the cellular and molecular mechanisms underlying the composition, heterogeneity, and formation of tumor immune microenvironments. Important genes such as LAYN and IGFLR1 also provided new options for future development of cancer therapeutics.