Abstract 5887: Association of ovarian tumor immune profiles with overall survival
Authors: Tworoger Shelley S. , Townsend Mary K. , Conejo-Garcia Jose , Fridley Brooke L. , Segura Carlos Moran , Saeed-Vafa Daryoush , Sasamoto Naoko , Terry Kathryn L. 
Published: June 2022

Abstract
Despite being immunogenic, high-grade serous ovarian carcinomas (HGSC), the most common histotype, generally are not responsive to immune checkpoint inhibitors. To understand potential reasons for this, we examined associations of tumor-infiltrating B cells and T cells, including sub-populations defined by expression of immune checkpoints and T cell exhaustion markers, with survival in three epidemiologic studies. Analyses included participants in the Nurses’ Health Study (NHS), NHSII, and New England Case-control study who were diagnosed with stage 1-3 HGSC for whom tumor tissue was obtained. B cells (CD19, CD20, CD138), T cells (CD3), and T cell subpopulations (CD3 co-localized with CD8, CD4, PD1, PDL1, LAG3, TIM3) were measured using multiplex immunofluorescence assays performed on tissue microarray slides containing 3 cores per case. For each participant, we summed counts of immune cells infiltrating the tumor and total tumor cells across cores. Counts of immune cell subpopulations were adjusted for the parent cell count using residuals from beta-binomial models. Hazard ratios (HR) and 95% confidence intervals (CI) for overall mortality according to presence/absence or quantiles of immune cells were calculated using Cox proportional hazards regression models adjusting for age at diagnosis, diagnosis year, stage, study, and total tumor cell count. Among 389 women with HGSC, presence vs. absence of CD19+ B cells was suggestively associated with lower mortality (HR 0.79, 95%CI:0.61-1.01); similar associations were observed for CD19-adjusted CD20+ B cells and CD138+ plasma cells (HRs 0.75-0.78, quintile 5 vs. 1).Higher total T cells was associated with improved survival (HR 0.67, 95%CI:0.45-0.99, quintile 5vs. 1). Similar reduced risks were observed with high levels of both CD19+ B cells and CD3+ T cells (HR 0.66) or high levels of one cell type (HRs 0.65-0.75) compared with low levels of both. For the two primary T cell subfractions, lower risk was observed with higher CD3-adjustedCD3+CD8+ cytotoxic T cells (HRs 0.68, 0.73, 0.69, 0.59 for quintiles 2-5 vs. 1), but notCD3+CD4+ helper T cells (HR 0.97, 95%CI: 0.72-1.31, tertile 3 vs. 1). T cells with immune checkpoint markers (PD1, PDL1) and/or markers of T-cell exhaustion (LAG3, TIM3) generally were not associated with mortality or tended to be associated with lower mortality risk, with a significant inverse association observed for CD3-adjusted CD3+PD1+TIM3- cells (HR 0.61,95%CI:0.41-0.92, quintile 5 vs. 1).Overall, higher levels of B cells and CD3+CD8+ T cells in tumor were associated with improved outcomes, consistent with other studies. Congruent with the apparent ineffectiveness of immune checkpoint inhibitors in ovarian cancer, our results do not support that T cells expressing immune checkpoint and/or T cell exhaustion markers are related to worse outcome among women with HGSC. Future analyses will consider multiple cell types simultaneously and the stroma compartment.
Citation Format: Shelley S. Tworoger, Mary K. Townsend, Jose Conejo-Garcia, Brooke L. Fridley, Carlos Moran Segura, Daryoush Saeed-Vafa, Naoko Sasamoto, Kathryn L. Terry. Association of ovarian tumor immune profiles with overall survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5887.