The Spatial Context of Tumor-Infiltrating Immune Cells Associates with Improved Ovarian Cancer Survival
Benjamin Steinhart, Kimberly R. Jordan, Jaidev Bapat, Miriam D. Post, Lindsay W. Brubaker, Benjamin G. Bitler, Julia Wrobel
Abstract
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.