Abstract PO-232: Racial differences in the tumor immune landscape and survival of high-grade serous ovarian carcinoma
Authors: Peres Lauren C , Colin-Leitzinger Christelle , Sinha Sweta , Marks Jeffrey R. , Conejo-Garcia Jose R. , Alberg Anthony J. , Bandera Elisa V. , Berchuck Andrew , Bondy Melissa L. , Christensen Brock C. , Cote Michele L. , Doherty Jennifer A. , Moorman Patricia G. , Segura Carlos Moran , Nguyen Jonathan V. , Peters Edward S. , Schwartz Ann G. , Terry Paul D. , Wilson Christopher M. , Fridley Brooke L. , Schildkraut Joellen M. 
Published: January 2022

Abstract
A survival benefit has been consistently observed for tumor infiltrating lymphocytes (TILs) among ovarian cancer patients; however, prior studies consist of predominantly white women and little work has been conducted in racially diverse cohorts. Here, we investigate racial differences in the tumor immune landscape and survival among African-American (AA) and white women with high-grade serous ovarian carcinoma (HGSOC), the most common histotype of ovarian cancer. Leveraging two population-based case-control studies of ovarian cancer, the African-American Cancer Epidemiology Study and the North Carolina Ovarian Cancer Study, treatment-naïve AA women with HGSOC were matched to white women with HGSOC by stage and age. Multiplex immunofluorescence staining was performed on formalin-fixed paraffin-embedded whole tissue sections to measure TILs (CD3+) and T-cell subsets, cytotoxic (CD3+CD8+) and regulatory (CD3+FoxP3+) T-cells. Image analysis was completed on three regions of interest (ROI) selected from the intratumoral region. We categorized immune cell abundance within the tumor, stroma, and overall as &lt;1% and ≥1% positive cells. Multivariable Cox proportional hazard regression models were used to examine the association between immune cell abundance and survival overall and by race. Among 121 AA and 121 white women with HGSOC, more than half (56%) had a higher TIL infiltrate overall, while 33% and 11% had higher levels of cytotoxic and regulatory T-cells, respectively. No differences in immune cell abundance were observed by race. Mean follow-up time was 4.3 ± 5.2 years, and 72% of the women are deceased. Higher levels of TILs and cytotoxic T-cells were associated with better outcomes overall (hazard ratio [HR]=0.68, 95% confidence interval [CI]=0.53, 0.88 and HR=0.59, 95% CI=0.44, 0.80, respectively) and these associations were similar irrespective of tumor/stroma. No association with survival was observed for T-regulatory cells overall and in the tumor; however, improved survival was noted for higher levels of T-regulatory cells in the stroma (HR=0.69, 95% CI=0.49, 0.96). Associations with survival among white women were consistent with the overall findings, but among AA women, all associations were attenuated and not statistically significant. For example, white women with higher overall TILs had a 42% lower risk of all-cause mortality (HR=0.58, 95% CI=0.41, 0.82), whereas the association among AA women was weaker and not statistically significant (HR=0.79, 95% CI=0.54, 1.17). Adjusting for frontline treatment did not substantively impact these findings. Our results add to the existing evidence that a robust TIL infiltrate confers a survival advantage among women with HGSOC; however, AA women may not experience the same survival benefit as white women with HGSOC. An external replication in a larger cohort of ovarian cancer patients and additional investigation, particularly further characterization of the T-cells (e.g., exhaustion, activation) and their co-localization with other prognostically relevant immune cells, is warranted.
Citation Format: Lauren C Peres, Christelle Colin-Leitzinger, Sweta Sinha, Jeffrey R. Marks, Jose R. Conejo-Garcia, Anthony J. Alberg, Elisa V. Bandera, Andrew Berchuck, Melissa L. Bondy, Brock C. Christensen, Michele L. Cote, Jennifer A. Doherty, Patricia G. Moorman, Carlos Moran Segura, Jonathan V. Nguyen, Edward S. Peters, Ann G. Schwartz, Paul D. Terry, Christopher M. Wilson, Brooke L. Fridley, Joellen M. Schildkraut. Racial differences in the tumor immune landscape and survival of high-grade serous ovarian carcinoma [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-232.