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

• Published in: Molecular cancer research 2021-12, Vol.19 (12), p.1973-1979
• Main Authors: Steinhart, Benjamin, Jordan, Kimberly R, Bapat, Jaidev, Post, Miriam D, Brubaker, Lindsay W, Bitler, Benjamin G, Wrobel, Julia
• Format: Article
• Language: English
• Subjects: Female; Humans; Lymphocytes, Tumor-Infiltrating - metabolism; Middle Aged; Ovarian Neoplasms - immunology; Ovarian Neoplasms - mortality; Survival Analysis
• ISSN: 1541-7786; 1557-3125
• DOI: 10.1158/1541-7786.MCR-21-0411

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 ( = 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.