PROJECT SUMMARY: Disparities in cancer outcomes in certain patient populations such as Hispanic/Latino (H/L) patients, are rooted in part in the lack of understanding of biologic factors and mechanisms of response or resistance to novel therapeutics. Although most patients express a willingness to participate in clinical research, only approximately 8% of adult cancer patients enroll in cancer clinical trials, and the percentage of minorities participating in clinical trials, overall, is much lower when compared to the general population of the U.S. H/L’s, and other minority groups, for example, continue to be under-represented in clinical trials. The under-representation of minority groups in cancer research contributes to disparities in cancer care and outcomes by failing to provide the evidence that clinicians and scientists need to safely treat and discover new treatments for minority patients with cancer. This project enables an integrative analysis of demographic, and clinical data combined with multi-omics approaches using blood samples and tissue from breast cancer patients to elucidate the differences in immune response to breast cancer in patients of H/L race. Immune checkpoint inhibition (ICI) is a type of immunotherapy that has revolutionized treatment for many patients with breast cancer. However, complex immunosuppressive tumor microenvironments (TMEs) within breast cancers render them less responsive to ICIs and present therapeutic obstacles. Specifically, recruitment of myeloid-derived suppressor cells (MDSCs) prohibit T-cell activation and infiltration which leads to successful treatment with this class of therapeutics. We aim to characterize differences in the suppressive TME by race and tumor subtype. Understanding these differences will affect development of novel treatment combinations & strategies. The identification of patient populations with higher risk disease, most likely to benefit from ICIs is of equal importance to understanding of scientific mechanisms. H/L patients have a higher percentage of young women (<50 years old) diagnosed with breast cancer and often with more aggressive subtypes as compared to Non-Hispanic White (NHW) patients. These differences persist even when correcting for socioeconomic factors. Overall, this work will help provide insight about differences in the immune TME in H/L patients with breast cancer and we will also try to determine if use of organoids could help screen for differences in efficacy with regard to development of one of our one clinical trials in development. We are investigating the promising therapeutic combination of a histone deacetylase inhibitor entinostat, combined with ICIs as this targets MDSCs. If we can determine a differential response to this treatment in H/L patient derived organoids this would provide a potential paradigm changing stratification of H/L patients with breast cancer who stand to benefit from the effects of this novel therapy.