Spatial Heterogeneity of Infiltrating T cells in High-Grade Serous Ovarian Cancer revealed by Multi-omics analysis

Abstract Tumor-infiltrating lymphocytes (TILs), especially CD8+ TILs, represent a favorable prognostic factor in high-grade serous ovarian cancer (HGSOC) and other tumor lineages. The spatial heterogeneity of different TIL subtypes in HGSOC remains to be elucidated. 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 patterns in ovarian cancer are identified: 1) ovarian lesions with low infiltration of mainly dysfunctional T cells and immunosuppressive Treg cells, 2) omental lesions infiltrated with non-tumor-specific bystander cells. Exhausted CD8 T cells that are preferentially enriched in ovarian tumors are clonal expanded and exhibit evidence for 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 informs potential strategies for therapeutic manipulation in HGSOC.