Unravelling the heterogeneity and dynamic relationships of tumor-infiltrating T cells by single-cell RNA sequencing analysis

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

article

Xin Yu¹  Lei Zhang²  Ashutosh Chaudhry¹  Aaron S. Rapaport¹  Wenjun Ouyang¹ 

[1] Department of Inflammation and Oncology, Amgen Research, Amgen Inc.;Beijing Advanced Innovation Center for Genomics, Peking-Tsinghua Center for Life Sciences, Peking University

关键词: cancer microenvironment;    exhausted T cells;    memory T cells;    regulatory T cells;    single-cell RNA sequencing;    TCR-based lineage tracing;    tumor-infiltrating T cells;   

DOI  :  10.1002/JLB.6MR0320-234R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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.

【 授权许可】

CC BY