Abstract 3968: Developing T cell and organoid co-cultures derived from breast cancer patients of African descent for drug screening

Abstract

Abstract Triple negative breast cancer (TNBC) is the most aggressive form of breast cancer. It is highly prevalent in women of West Sub-Saharan African ancestry (WSSA) and African American (AA) women, resulting in poorer survival outcomes compared to European American (EA) women. Studies have shown that immune cells in the tumor microenvironment (TME) contribute to the progression of TNBC by immune suppression, the reprogramming of macrophages into pro-tumorigenic subtypes and the release of inflammatory cytokines. A previous study by our laboratory revealed that the immune processes and markers associated with TNBC are different in TNBC patients of African ancestry compared to EA patients. We have established platforms consisting of T cells co-cultured with organoids derived from patients of diverse ancestries to investigate the interactions between immune cells and TNBC cells. Organoids from Ghanaian (GH), EA and AA patients were successfully established from PDXs and primary tumors. T cells were isolated from patient PBMCs (matched tumor and T-cell), activated and tested in co-cultures with organoids, derived from TNBC tumors. Flow cytometry was performed to assess the efficacy of T cell killing. The activated T cells successfully eradicated TNBC cells at conditions that replicate in vivo T cell infiltration in TNBC, as evidenced by decreased percentages of EpCAM+ cells. Concomitantly, we observed a reduction in the percentages of CD3+ CD137+ activated T cells, suggesting that the tumor cells in the co-culture also impacted T cells. Based on our initial results, we are evaluating the effects of co-culture on distinct populations of cytotoxic T cells as well as on markers of activation and exhaustion to determine potential differences between TNBC patients of diverse ethnicities. Characterizing the differences in tumor-immune cell interactions within the TNBC tumor microenvironment between EA and AA TNBC patients will hopefully inform the development of novel therapeutic strategies for women of African descent. Citation Format: Batoul Farran, Moses Kamita, Sylvester Antwi, Valerie Ofori Abohah, Harriet Larrious-Lartey, Jessica Bensenhaver, Haythem Ali, Eleonor Walker, Foster Amponsah, Josephine Nsaful, Rose Dampson, Patrick Kafui Akakpo, Evelyn Jiagge. Developing T cell and organoid co-cultures derived from breast cancer patients of African descent for drug screening [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3968.