Spatial Heterogeneity of Infiltrating T Cells in High-Grade Serous Ovarian Cancer Revealed by Multi-omics Analysis

Authors

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

Publication Date

12-20-2022

Journal

Cell Reports Medicine

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

Humans, Female, Ovarian Neoplasms, Prognosis, Multiomics, Ovarian Cysts, Receptors, Antigen, T-Cell, Tumor Microenvironment, PMID: 36543113

Comments

Associated Data

PMID: 36543113