The spatial structure of the tumor immune microenvironment can explain and predict patient response in high-grade serous carcinoma

Abstract

Despite ovarian cancer being the deadliest gynecological malignancy, there has been little change to therapeutic options and mortality rates over the last three decades. Recent studies indicate that the composition of the tumor immune microenvironment (TIME) influences patient outcomes but are limited by a lack of spatial understanding. We performed multiplexed ion beam imaging (MIBI) on 83 human high-grade serous carcinoma tumors -- one of the largest protein-based, spatially-intact, single-cell resolution tumor datasets assembled -- and used statistical and machine learning approaches to connect features of the TIME spatial organization to patient outcomes. Along with traditional clinical/immunohistochemical attributes and indicators of TIME composition, we found that several features of TIME spatial organization had significant univariate correlations and/or high relative importance in high-dimensional predictive models. The top performing predictive model for patient progression-free survival (PFS) used a combination of TIME composition and spatial features. Results demonstrate the importance of spatial structure in understanding how the TIME contributes to treatment outcomes. Furthermore, the present study provides a generalizable roadmap for spatial analyses of the TIME in ovarian cancer research.