Spatial heterogeneity of infiltrating T cells in high-grade serous ovarian cancer revealed by multi-omics analysis

Bin Yang; Xiong Li; Wei Zhang; Junpeng Fan; Yong Zhou; Wenting Li; Jingjing Yin; Xiaohang Yang; Ensong Guo; Xi Li; Yu Fu; Si Liu; Dianxing Hu; Xu Qin; Yingyu Dou; Rourou Xiao; Funian Lu; Zizhuo Wang; Tianyu Qin; Wei Wang; Qinghua Zhang; Shuaicheng Li; Ding Ma; Gordon B Mills; Gang Chen; Chaoyang Sun

doi:10.1016/j.xcrm.2022.100856

Spatial heterogeneity of infiltrating T cells in high-grade serous ovarian cancer revealed by multi-omics analysis

Cell Rep Med. 2022 Dec 20;3(12):100856. doi: 10.1016/j.xcrm.2022.100856.

Authors

Bin Yang¹, Xiong Li², Wei Zhang³, Junpeng Fan¹, Yong Zhou³, Wenting Li¹, Jingjing Yin¹, Xiaohang Yang¹, Ensong Guo¹, Xi Li¹, Yu Fu¹, Si Liu¹, Dianxing Hu¹, Xu Qin¹, Yingyu Dou¹, Rourou Xiao¹, Funian Lu¹, Zizhuo Wang¹, Tianyu Qin¹, Wei Wang⁴, Qinghua Zhang², Shuaicheng Li³, Ding Ma¹, Gordon B Mills⁵, Gang Chen⁶, Chaoyang Sun⁷

Affiliations

¹ Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
² Department of Gynecology & Obstetrics, the Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
³ City University of Hong Kong, Shenzhen Research Institute, Shenzhen 518083, China.
⁴ Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: 951102572@qq.com.
⁵ Department of Cell, Development and Cancer Biology, Oregon Health and Sciences University, Portland, OR 97201, USA; Knight Cancer Institute, Portland, OR 97201, USA; Department of Systems Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
⁶ Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: gumpc@126.com.
⁷ Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: suncydoctor@gmail.com.

Abstract

Tumor-infiltrating lymphocytes (TILs), especially CD8⁺ TILs, represent a favorable prognostic factor in high-grade serous ovarian cancer (HGSOC) and other tumor lineages. Here, we analyze the spatial heterogeneity of different TIL subtypes in HGSOC. We integrated RNA sequencing, whole-genome sequencing, bulk T cell receptor (TCR) sequencing, as well as single-cell RNA/TCR sequencing to investigate the characteristics and differential composition of TILs across different HGSOC sites. Two immune "cold" patterns in ovarian cancer are identified: (1) ovarian lesions with low infiltration of mainly dysfunctional T cells and immunosuppressive Treg cells and (2) omental lesions infiltrated with non-tumor-specific bystander cells. Exhausted CD8 T cells that are preferentially enriched in ovarian tumors exhibit evidence for expansion and cytotoxic activity. Inherent tumor immune microenvironment characteristics appear to be the main contributor to the spatial differences in TIL status. The landscape of spatial heterogeneity of TILs may inform potential strategies for therapeutic manipulation in HGSOC.

Keywords: TILs; high-grade serous ovarian cancer; multi-omics; multiple lesions; spatial heterogeneity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Female
Humans
Multiomics
Ovarian Cysts*
Ovarian Neoplasms* / genetics
Ovarian Neoplasms* / pathology
Prognosis
Receptors, Antigen, T-Cell / genetics
Tumor Microenvironment / genetics

Substances

Receptors, Antigen, T-Cell