Identification of shared characteristics in tumor-infiltrating T cells across 15 cancers

Xiyun Jin; Yideng Cai; Guangfu Xue; Jinhao Que; Rui Cheng; Yuexin Yang; Lixing Xiao; Xiaoyu Lin; Chang Xu; Pingping Wang; Zhaochun Xu; Huan Nie; Qinghua Jiang

doi:10.1016/j.omtn.2023.03.007

Identification of shared characteristics in tumor-infiltrating T cells across 15 cancers

Mol Ther Nucleic Acids. 2023 Mar 21:32:189-202. doi: 10.1016/j.omtn.2023.03.007. eCollection 2023 Jun 13.

Authors

Xiyun Jin¹, Yideng Cai¹, Guangfu Xue¹, Jinhao Que¹, Rui Cheng¹, Yuexin Yang¹, Lixing Xiao¹, Xiaoyu Lin¹, Chang Xu¹, Pingping Wang², Zhaochun Xu¹, Huan Nie¹, Qinghua Jiang^{1

2

3}

Affiliations

¹ School of Life Science and Technology, Harbin Institute of Technology, Harbin 150000, China.
² School for Interdisciplinary Medicine and Engineering, Harbin Medical University, Harbin 150076, China.
³ Key Laboratory of Biological Big Data of the Ministry of Education, Harbin Institute of Technology, Harbin 150000, China.

Abstract

Tumor-infiltrating T cells are essential players in tumor immunotherapy. Great progress has been achieved in the investigation of T cell heterogeneity. However, little is well known about the shared characteristics of tumor-infiltrating T cells across cancers. In this study, we conduct a pan-cancer analysis of 349,799 T cells across 15 cancers. The results show that the same T cell types had similar expression patterns regulated by specific transcription factor (TF) regulons across cancers. Multiple T cell type transition paths were consistent in cancers. We found that TF regulons associated with CD8⁺ T cells transitioned to terminally differentiated effector memory (Temra) or exhausted (Tex) states were associated with patient clinical classification. We also observed universal activated cell-cell interaction pathways of tumor-infiltrating T cells in all cancers, some of which specifically mediated crosstalk in certain cell types. Moreover, consistent characteristics of TCRs in the aspect of variable and joining region genes were found across cancers. Overall, our study reveals common features of tumor-infiltrating T cells in different cancers and suggests future avenues for rational, targeted immunotherapies.

Keywords: MT: Bioinformatics; T cell receptor; TF regulon; cell-cell communication; pan-cancer; single-cell sequencing; state transition; tumor-infiltrating T cells.