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 WangQinghua Zhang, Shuaicheng Li, Ding Ma, Gordon B. Mills, Gang Chen, Chaoyang Sun

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Article number100856
JournalCell Reports Medicine
Issue number12
StatePublished - Dec 20 2022


  • TILs
  • high-grade serous ovarian cancer
  • multi-omics
  • multiple lesions
  • spatial heterogeneity

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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