Spatial tumor immune microenvironment phenotypes in ovarian cancer

Abstract

Immunotherapy has largely failed in ovarian carcinoma (OC), likely due to that the vast tumor heterogeneity and variation in immune response have hampered clinical trial outcomes. Tumor-immune microenvironment (TIME) profiling may aid in stratification of OC tumors for guiding treatment selection. Here, we used Digital Spatial Profiling to characterize regions of spatially distinct TIME phenotypes in OC. Tumors with diffuse immune-infiltration and increased tumor-immune spatial interactions have higher presence of IDO1, PD-L1, PD-1 and Tim-3, while focal immune niches had higher CD163 macrophages and a preliminary worse outcome. Immune exclusion was associated with presence of Tregs and activated fibroblasts. High-grade serous OC showed an overall stronger immune response and presence of multiple targetable checkpoints. Low-grade serous OC was associated with high expression of STING and endometrioid ovarian carcinoma had higher presence of CTLA-4. Mucinous and clear cell OC were dominated by focal immune clusters and immune-excluded regions, with mucinous tumors displaying T-cell rich immune niches, and clear cell tumors an overall low immune activation.