Abstract PR006: Association of multi-level stress-related determinants with the local and systemic tumor immune environment in Black and White women with breast cancer
Authors: Harris Alexandra R. , Pichardo Catherine M. , Franklin Jamirra , Liu Huaitian , Wooten William , Panigrahi Gatikrushna , Lawrence Wayne R. , Pichardo Margaret S. , Jenkins Brittany D. , Acevedo Amanda M. , Dorsey Tiffany H. , Agurs-Collins Tanya , Ambs Stefan 
Published: September 2024

Abstract
Importance: Exposure to chronic stress have been implicated as a contributor to disparities in cancer risk and outcomes. Yet, the biological mechanisms underlying their influence on tumor biology and the immune microenvironment remain poorly understood. Objective: To investigate the genomic, transcriptomic, and proteomic impact of multi-level stress-related measures (chronic stress, racial and ethnic discrimination, inadequate social support, and neighborhood deprivation) on tumor biology and the local and systemic immune environment of White and Black/AA women with breast cancer. Design, Setting, and Participants: A cross-sectional study was conducted from 2012-2023, collecting 117 blood samples, 51 breast tumors, and 41 adjacent non-cancerous tissues from women with breast cancer. Participants were recruited through the University of Maryland Medical Center, Baltimore, Maryland, and completed demographic and psychosocial questionnaires. Exposures: Perceived stress; racial and ethnic discrimination; social support; and 2010 census tract-level neighborhood deprivation. Main Outcomes and Measures: Tumor mutational burden; breast tissue gene expression; tumor immune cell profiles; and levels of 92 circulating immune-oncology markers and associated pathways. Results: Chronic stress, but not other exposures, showed an association with high tumor mutational burden (𝛃=0.018, p=0.059). While greater social support was associated with more favorable, immune-stimulatory changes (e.g. activated NK cells in tumors of Black/AA women; increased serum IL-5 [𝛃=0.06, p=0.003]), exposure to chronic stress, discrimination, and neighborhood deprivation tended to associate with aggressive tumor biology (e.g. enrichment of signaling pathways related to proliferation, cellular stress, and hypoxia), deleterious immune cell profiles (e.g., tumor-associated M2 macrophages, 𝛃=0.82, p=0.02), systemic inflammation (e.g. increased levels of serum IL6 [𝛃=0.68, p=0.014], TNFSF12A [𝛃=0.61, p=0.034]), and suppression of the antitumor immune response (𝛃=0.37, p=0.051). Race-stratified analyses showed that the negative biological impact of these stressors was more pronounced in Black/AA women. Conclusions and Relevance: Chronic stress, discrimination, inadequate social support, and neighborhood deprivation were associated with deleterious biological and immunological alterations to the local and systemic tumor immune environment in women with breast cancer, particularly for Black/AA women.
Citation Format: Alexandra R. Harris, Catherine M. Pichardo, Jamirra Franklin, Huaitian Liu, William Wooten, Gatikrushna Panigrahi, Wayne R. Lawrence, Margaret S. Pichardo, Brittany D. Jenkins, Amanda M. Acevedo, Tiffany H. Dorsey, Tanya Agurs-Collins, Stefan Ambs. Association of multi-level stress-related determinants with the local and systemic tumor immune environment in Black and White women with breast cancer [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr PR006.