Spatial Clustering of Recently Activated Cytotoxic Lymphocytes Improves Association with Overall Survival in Women with High-Grade Serous Ovarian Cancer

BACKGROUND: A previous study found that adding the spatial context of tumor-infiltrating lymphocytes (TIL) and cytotoxic T lymphocytes (CTL) to abundance improved associations with overall survival (OS) of non-Hispanic Black women with high-grade serous ovarian cancer (HGSOC). This study set out to replicate previous findings in predominantly non-Hispanic White women HGSOC cohorts. METHODS: Multiplex immunofluorescence was used to characterize TILs in HGSOC from women enrolled in three epidemiologic studies (N = 433). Spatial clustering of TILs was derived using a permutation approach for Ripley K. Cox proportional hazards models were used for associations of spatial clustering and abundance with OS. RESULTS: In models assessing differences in spatial clustering within tumors with a high abundance of TILs (>1%), we found that spatial information significantly improved the model fit for the recently activated CTLs (likelihood ratio test P = 0.008), in which low spatial clustering in high abundance was associated with a decreased risk of mortality (hazard ratio = 0.31; 95% confidence interval, 0.14-0.70; P = 0.004) compared with when the recently activated CTLs were highly clustered. CONCLUSIONS: In this study, we replicated the significantly improved association with OS in mostly White women with HGSOC by including spatial information for the recently activated CTLs. Further research is needed to understand the mechanisms by which recently activated spatial architecture affects survival from HGSOC. IMPACT: This study validates our previous findings that adding spatial context to abundance, especially CTLs or the recently activated CTLs, when performing survival analyses improves the fit of the models.