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Unravelling the heterogeneity and dynamic relationships of tumor‐infiltrating T cells by single‐cell RNA sequencing analysis
Author(s) -
Yu Xin,
Zhang Lei,
Chaudhry Ashutosh,
Rapaport Aaron S.,
Ouyang Wenjun
Publication year - 2020
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.6mr0320-234r
Subject(s) - biology , immune checkpoint , transcriptome , tumor microenvironment , immune system , t cell , single cell sequencing , t cell receptor , effector , cancer immunology , computational biology , cell , cancer research , immunotherapy , gene , immunology , genetics , phenotype , gene expression , exome sequencing
T cells are crucial for the success of immune‐based cancer therapy. Reinvigorating antitumor T cell activity by blocking checkpoint inhibitory receptors has provided clinical benefits for many cancer patients. However, the efficacy of these treatments varies in cancer patients and the mechanisms underlying these diverse responses remain elusive. The density and status of tumor‐infiltrating T cells have been shown to positively correlate with patient response to checkpoint blockades. Therefore, further understanding of the heterogeneity, clonal expansion, migration, and effector functions of tumor‐infiltrating T cells will provide fundamental insights into antitumor immune responses. To this end, recent advances in single‐cell RNA sequencing technology have enabled profound and extensive characterization of intratumoral immune cells and have improved our understanding of their dynamic relationships. Here, we summarize recent progress in single‐cell RNA sequencing technology and current strategies to uncover heterogeneous tumor‐infiltrating T cell subsets. In particular, we discuss how the coupling of deep transcriptome information with T cell receptor (TCR)‐based lineage tracing has furthered our understanding of intratumoral T cell populations. We also discuss the functional implications of various T cell subsets in tumors and highlight the identification of novel T cell markers with therapeutic or prognostic potential.