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

Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved..

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2022

Erschienen:

2022

Enthalten in:

Zur Gesamtaufnahme - volume:3

Enthalten in:

Cell reports. Medicine - 3(2022), 12 vom: 20. Dez., Seite 100856

Sprache:

Englisch

Beteiligte Personen:

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

Links:

Volltext

Themen:

High-grade serous ovarian cancer
Journal Article
Multi-omics
Multiple lesions
Receptors, Antigen, T-Cell
Research Support, Non-U.S. Gov't
Spatial heterogeneity
TILs

Anmerkungen:

Date Completed 23.12.2022

Date Revised 08.01.2023

published: Print

Citation Status MEDLINE

doi:

10.1016/j.xcrm.2022.100856

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM350546975