Abstract C072: Evidence of more highly activated anti-tumor immunity in Hispanic/Latinx patients with breast cancer and associated social determinants of health

Abstract Background: Breast cancer is the leading cause of cancer-related death among Hispanic/Latinx (H/L) women in the U.S. Compared to Non-Hispanic White (NHW) women, H/L patients are more likely to be diagnosed before age 50 (29% vs. 15%), to present with larger tumors (2.0 cm in 45% vs. 38%) and to have estrogen receptor (ER)-negative subtypes (18% vs. 14%). All patients with breast cancer have low levels of anti-tumor immunity as a result of intrinsic immune suppression, affecting response to standard therapies, including immunotherapy. We hypothesize that biological and social factors interact to shape an immunosuppressive tumor microenvironment, which can lead to disparities in clinical outcomes. Preliminary investigation of circulating and intratumoral immune cells in parallel with social determinants of health (SDOH) assessments suggest possible correlations between disparities in SDOH and preliminary differences in anti-tumor immunity. Methods: Bulk RNA sequencing (for immune cell fractions), whole exome sequencing (for common mutations), PD-L1 status (for combined positivity scores), and self-reported race and clinical outcomes (by disease biopsy site and histological subtype) were collected for 7,000 patients via collaboration with Caris Life Sciences. We performed multiparametric flow cytometry of peripheral blood samples to characterize circulating immune populations from an additional 130 patients. Spatial transcriptomics were used to profile intratumoral immunity on 13 patients via Visium 10X. A social deprivation index (SDI) was calculated based on patient zip codes and additional demographic factors for 130 patients. Descriptive statistics were used to summarize demographics, tumor characteristics, and SDI components. Results: H/L patients exhibited shorter overall median survival, higher PD-L1 positivity, and higher interferon-gamma score in those whom primary breast tumors were examined. Moreover, we observed an enrichment of circulating myeloid-derived suppressor cells (MDSCs), exhausted CD8+ T cells, and M2-polarized macrophages, consistent with an immunosuppressive immune profile. Spatial localization and transcriptomic data from H/L patients showed greater intratumoral lymphocyte infiltration. SDI scores were higher among H/L patients, relative to NHW. Across both H/L and NHW groups, higher SDI correlated with increased circulating G-MDSCs and regulatory T cells. Within the H/L group, circulating CD8+ and CD4+ T-cell levels also increased with greater deprivation. Conclusions: Poorer clinical outcomes were observed in H/L patients who also demonstrated higher levels of pro- and anti-tumor immune activation. These immune-related disparities are likely influenced by both biological mechanisms and contextual social disadvantage. Ongoing work includes validating these findings in larger genomic datasets and stratifying by histologic subtype. Addressing differences in tumor immune microenvironment and social vulnerability is essential to providing personalized treatment options to improve outcomes in patients with breast cancer. Citation Format: Nana A. K. Gyabaah-Kessie, Elexa Rallos, Sachin Kumar Deshmukh, Joel Sanchez Mendez, Diego I. Alvarez-Lopez, Dominic Zavala, Batul Al-Zubeidy, Matthew Jacobo, Michelle Li, Sabrina Carrel, George Sledge, David Conti, Robert Hsu, Mariana C. Stern, Evanthia T. Roussos Torres. Evidence of more highly activated anti-tumor immunity in Hispanic/Latinx patients with breast cancer and associated social determinants of health abstract. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr C072.