Abstract B023: Ovarian cancer tumor associated macrophages and tumor infiltrating lymphocytes in the stromal compartment associated with intrauterine device and oral contraception use

Abstract Introduction: Oral contraceptives (OC) strongly protect against ovarian cancer, however, OC use has been declining while intrauterine device (IUD) use is increasing and the impact of this shift on ovarian cancer risk is largely unknown. IUD use may increase local inflammation, leading to alteration of immune microenvironment profiles whereas OC use causing ovulation cessation may be associated with reduced local inflammation. As chronic inflammation may contribute to immunosuppressive tumor microenvironment, we hypothesized that IUD use may be associated with a more immunosuppressive tumor microenvironment compared to OC use, which may be more evident in the stromal components of the tumor. Therefore, we assessed the associations of tumor-associated macrophages (TAMs) and tumor-infiltrating lymphocytes (TILs) in the stromal cells of the tumor with contraception use to better understand their influence on ovarian cancer carcinogenesis. Methods: We used ovarian tumor samples embedded into tissue microarrays (TMAs) and questionnaire data from multiple studies (African American Cancer Epidemiology Study, Diseases of the Ovary and their Evaluation, Hormone and Ovarian Cancer Prediction, New England Case Control Study, and Nurses’ Health Studies I and II). TAMs (CD68+, M1+, M2+, M0+) and TILs (CD3+, CD3+CD8+, CD3+CD4+FOXP3+) were assessed using multiplex immunofluorescence (mIF). Contraception use was self-reported as ever used an IUD (predominant non-hormonal) and/or OC. We used beta binomial models to calculate odds ratios (OR) and 95% confidence intervals (CI) for stromal cell positivity for TAM and TIL markers in association with IUD and OC use, adjusting for age at cancer diagnosis, parity, family history of breast or ovarian cancer, histotype, study site, and mutually adjusting for contraception method. Results: Of the 1,801 cases included in the study, 314 had ever used IUD (17.4%) and 924 had ever used OC for at least one year (51.3%). Overall, there were no statistically significant associations between abundance of different immune markers in the stroma with ever use of IUD or OC. However, ever use of IUD was associated with a higher odds of CD3+CD8+ positivity (OR: 1.08, CI: 0.94-1.24), while ever use of OC was associated with lower odds of CD3+CD8+ (OR: 0.92, CI: 0.83-1.03; p-het=0.07). Conclusions: We observed no statistically significant associations of contraception use with TAMs and TILs in the stromal component of the tumor microenvironment. Ongoing analyses include examination of modifiers contributing to inflammation, including body mass index and endometriosis. Additional analyses will assess duration and timing of OC and IUD use, potential modification by parity, as well as differences in the tumor microenvironment by histotype. Citation Format: Jennifer M. Mongiovi, Roshni Babel, Ellie Lee, Ana Babic, Naoko Sasamoto, Mary K. Townsend, Allison F. Vitonis, Mollie Barnard, Jonathan Hecht, T. Rinda Soong, Lauren C. Peres, Joellen M. Schildkraut, Holly R. Harris, Jennifer A. Doherty, Francesmary Modugno, Brooke L. Fridley, Shelley S. Tworoger, Kathryn L. Terry. Ovarian cancer tumor associated macrophages and tumor infiltrating lymphocytes in the stromal compartment associated with intrauterine device and oral contraception use [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Ovarian Cancer Research; 2025 Sep 19-21; Denver, CO. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl):Abstract nr B023.