Abstract C115: Chromatin acetylation at H3K9ac, inflammatory signaling, and evidence for immune cell senescence in Los Angeles women with insulin-resistance

Abstract

Abstract Insulin-resistance (IR) is a known risk factor for diabetes and has been shown to lead to epigenetic dysregulation, such as inappropriate chromatin opening, and inflammation. In Los Angeles one-third of Young Women of Color are insulin-resistant, making them at risk for Type- 2 Diabetes, and triple negative breast cancer. In our current study we tested 28 women living in Los Angeles for insulin-resistance, chromatin acetylation, and tissue inflammation. Our ChIP- seq studies provide evidence that in IR women, there is increased acetylation of H3K9ac at the promoters of IL6, TNFα, and NFkB/IRF1 (regulator in INF-beta signaling). Cytokine arrays corroborate these findings and show increased production of INFβ, IL6, and TNFα. Interestingly IL6 and TNFα are known cytokines excreted by a senescence-associated secretory phenotype (SASP) factors. Additionally, NFkB is a mediator of SASP induction, which prompted us to investigate senescence in these women. We found that in IR women there is an increase in senescent naïve CD4 T cells and CD4 T helper 1 (Th1) and Th17 cells. Given the important role that inflammation and senescence has on cancer initiation and progression, our findings provide a potential link between insulin-resistance, inflammation/senescence, and cancer. Citation Format: Christina M. Vidal, Jackelyn A. Alva-Ornelas, Parijat Senapati, Jerneja Tomsic, Victoria L. Seewaldt. Chromatin acetylation at H3K9ac, inflammatory signaling, and evidence for immune cell senescence in Los Angeles women with insulin-resistance [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 C115.