The Spatial Context of Tumor-Infiltrating Immune Cells Associates with Improved Ovarian Cancer Survival

Mol Cancer Res. 2021 Dec;19(12):1973-1979. doi: 10.1158/1541-7786.MCR-21-0411. Epub 2021 Oct 6.

Abstract

Ovarian cancer is the deadliest gynecologic malignancy. Multi-omics techniques have provided a platform for improved predictive modeling of therapy response and patient outcomes. While high-grade serous carcinoma (HGSOC) tumors are immunogenic and numerous studies have defined positive correlation to immune cell infiltration, immunotherapies in clinical trials have exhibited low efficacy rates. There is a significant need to better comprehend the role and composition of immune cells in mediating ovarian cancer therapeutic response and progression. We performed multiplex IHC with an HGSOC tissue microarray (n = 127) to characterize the immune cell composition within tumors. After analyzing the composition and spatial context of T cells (CD4/CD8), macrophages (CD68), and B cells (CD19) within the tumor, we found that increased B-cell and CD4 T-cell presence correlated with overall survival. More importantly, we observed that the proximity between tumor-associated macrophages and B cells or CD4 T cells significantly correlated with overall survival. IMPLICATIONS: The results highlight the antitumor role of B cells and CD4 T cells, and that the spatial interactions between immune cell types are a novel predictor of therapeutic response and patient outcomes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Female
  • Humans
  • Lymphocytes, Tumor-Infiltrating / metabolism*
  • Middle Aged
  • Ovarian Neoplasms / immunology*
  • Ovarian Neoplasms / mortality
  • Survival Analysis