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.
基金:
National Key R&D Program of China [2022YFC2704200, 2022YFC2704202, 2016YFC1303100]; Nature and Science Foundation of China [81572569, 81874106, 81402163, 81974408]; Wuhan Municipal Health Commission [WX18Q16]
第一作者单位:[1]Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Obstet & Gynecol, Wuhan 430030, Peoples R China
通讯作者:
推荐引用方式(GB/T 7714):
Yang Bin,Li Xiong,Zhang Wei,et al.Spatial heterogeneity of infiltrating T cells in high- grade serous ovarian cancer revealed by multi-omics analysis[J].CELL REPORTS MEDICINE.2022,3(12):doi:10.1016/j.xcrm.2022.100856.
APA:
Yang, Bin,Li, Xiong,Zhang, Wei,Fan, Junpeng,Zhou, Yong...&Sun, Chaoyang.(2022).Spatial heterogeneity of infiltrating T cells in high- grade serous ovarian cancer revealed by multi-omics analysis.CELL REPORTS MEDICINE,3,(12)
MLA:
Yang, Bin,et al."Spatial heterogeneity of infiltrating T cells in high- grade serous ovarian cancer revealed by multi-omics analysis".CELL REPORTS MEDICINE 3..12(2022)