Impact of spatial clustering of cytotoxic and tumor infiltrating lymphocytes on overall survival in women with high grade serous ovarian cancer

Abstract

AbstractBackgroundStudies have shown that tumor infiltrating lymphocyte (TILs) abundance is associated with overall survival in patients with high-grade serous ovarian cancer (HGSOC); however, the role of the spatial contexture and organization of TILs is less clear.MethodsWe evaluated the association between spatial architecture of T cells and survival in women with HGSOC from three large epidemiological studies in which tumors were analyzed by multiplex immunofluorescence (N = 433). A Ripley’sKmeasure was used to determine the spatial clustering. Cox proportional hazards models assessed the association of spatial clustering with overall survival.ResultsWe found having high abundance and low spatial clustering of CD3+TILs and CD3+CD8+cytotoxic T lymphocytes (CTLs) was associated with improved overall survival (TILs HR=0.61, 95% CI 0.46-0.81,P=0.0005; CTLs HR=0.59, 95% CI 0.44-0.80,P=0.0007). Models with abundance and spatial information outperformed models with only the abundance levels (TILsP=0.002, CTLsP=0.00007).ConclusionHigh abundance of TILs and CTLs that are spatially distributed across the tumor was associated with better survival, replicating our work in non-Hispanic Black women, and supporting that the spatial architecture of the tumor microenvironment is an important predictor of survival in HGSOC.