Abstract 2506: The influence of sex on the immune microenvironment in male and female breast cancer

Abstract

Even when accounting for multiple clinical parameters, male breast cancer patients have significantly lower survival rates than females. Males and females differ in their levels of sex hormones androgens and estrogens. These sex hormones have varying influences on immune cell populations, which in turn may affect disease progression. Thus, the sex of the patient and the levels of sex hormones are likely important for anticancer immunity. Here, we assessed the importance of sex hormone signaling in the immune cells (host) versus the tumor cells for defining the immune landscape associated with primary and metastatic tumors. We used flow cytometry to determine the immune profile of mammary tumors, spleens, and lungs, and histochemistry to evaluate metastasis in transgenic MMTV-PyMT and in mice orthotopically injected with sex-specific MMTV-PyMT-derived cell lines in male and female cohorts. In transgenic mice, males had greater proportions of CD4+ T-helper and total myeloid cells in all organs analyzed. The splenic and pulmonary immune profiles of tumor-bearing males were more similar to cancer-free littermates than in females. Interestingly, males trended towards increased metastatic colonization in the lungs. Sex-associated immune profiles differed between transgenic and orthotopic mice. In mice bearing male-derived R221a PyMT tumors, females had decreased intratumoral neutrophils and elevated natural killer cells with increased splenic B-cells in comparison to males. Overall, our data supports a sex-dependent immune response in mammary carcinoma that is, in part, regulated by the hormonal environment of the host. With emerging therapeutics targeting the tumor immune microenvironment, characterization of immune profiles is critical for optimizing their use in all breast cancer patients. Citation Format: Ebony Hargrove-Wiley, Barbara Fingleton. The influence of sex on the immune microenvironment in male and female breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2506.