Abstract
Background: Blacks tend to have a stronger inflammatory immune response than Whites. We hypothesized that racial differences in host immunity also manifest in the tumor microenvironment (TME), constituting part of a distinct tumor biology underlying more aggressive breast cancer and higher mortality in Black women.
Patients and Methods: Pathologic and gene expression profiling approaches were used for comprehensively characterizing infiltrating immune cells in breast TME from 1,315 patients from the Women’s Circle of Health Study (WCHS). Racial differences in tumor immune phenotypes were compared, with results validated in data from The Cancer Genome Atlas (TCGA). Prognostic associations of immune phenotypes were assessed in WCHS, TCGA and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) cohorts.
Results: We found marked and consistent differences in tumor immune responses between Black and White patients. Not only did tumors from Blacks display a stronger overall immune presence, but the composition and quality of immune infiltrates differed, independent of tumor subtypes. Black patients had a stronger humoral immunity response, and further, a more exhausted CD8+ T-cell profile featuring the coexpression of PD-1, LAG3, and CTLA4. A signature indicating a higher ratio of exhausted CD8+ T cells to total CD8+ T cells (ExCD8-r) was consistently associated with poorer survival, particularly among hormone receptor-positive patients. Combinations of the absolute fraction of CD8+ T cells and ExCD8-r signature identified the CD8-low/ExCD8-r-high subgroup, the most prevalent among Blacks, as having the worst survival.
Conclusions: Our findings of a distinct exhausted CD8+ T-cell signature in Black breast cancer patients indicates an immunobiologic basis for their more aggressive disease, and also a rationale for the use of immune checkpoint inhibitors targeting the exhaustion phenotype.
Citation Format: Song Yao, Ting-Yuan Cheng, Ahmed Elkhanany, Li Yan, Angela Omilian, Scott I. Abrams, Sharon Evans, Chi-Chen Hong, Qianya Qi, Warren Davis, Song Liu, Elisa V. Bandera, Kunle Odunsi, Kazuaki Takabe, Thaer Khoury, Christine B. Ambrosone. Breast tumor microenvironment in black women: A distinct signature of CD8+ T-cell exhaustion [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr IA26.
