Extensive exploration of T cell heterogeneity in cancers by single cell sequencing.

Xiaofang Wang,Yangqiu Li

doi:10.21147/j.issn.1000-9604.2019.02.15

Abstract

Human T cells are a highly heterogeneous population and can recognize a wide variety of antigens by their T cell receptors (TCRs). Tumor cells display a large repertoire of antigens that serve as potential targets for recognition, thus making T cells in the tumor micro-environment more complicated. Making a connection between TCRs and the transcriptional information of individual T cells will be interesting for investigating clonal expansion within T cell populations under pathologic conditions. Advances in single cell RNA-sequencing (scRNA-seq) have allowed for comprehensive analysis of T cells. In this review, we briefly describe the research progress on tumor micro-environment T cells using single cell RNA sequencing, and then discuss how scRNA-seq can be used to resolve immune system heterogeneity in health and disease. Finally, we point out future directions in this field and potential for immunotherapy.

Highlights

Human immune system is composed of multiple cells that coordinately protect against various pathogens
Before the development of scRNA-seq, the discovery of new cell subsets involved using cell surface markers. scRNA-seq opens up a new era in which we can construct a T cell atlas from normal and tumor tissues or cancerous lymph nodes, revealing the diversity in the tumor micro-environment, discovering variations in gene expression, and building developmental trajectories
T cells are heterogeneous in tumors, and Tregs are usually enriched, while CD8+ T cells become exhausted tumor-infiltrating lymphocytes (TILs) or TRM cells in tumors

Summary

Introduction

Human immune system is composed of multiple cells that coordinately protect against various pathogens. It has been reported that significant heterogeneity in the immune composition is observed across tumor subtypes and patients with breast cancer [22]. Many research groups have studied transcriptional maps of T cells in different tumors using scRNA-seq. Researchers from Memorial Sloan Kettering Cancer Center profiled 45,000 immune cells from 8 breast carcinomas and matched normal breast tissue, blood, and lymph nodes. This group derived an immune map of breast cancer, pointing to continuous T cell activation and differentiation states [35].

Method

Conclusions

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Key findings