Abstract 4973: Comparison of tumor immune microenvironment in triple negative breast cancer (TNBC) of African American versus that of white patients

Abstract

Abstract Introduction: Although there are many possible causes, it has been observed that Triple Negative Breast Cancer (TNBC) has a worse overall outcome in African American (AA) than white patients. Recently, there is also evidence that the patients response to the tumor, or the biological response expressed as the tumor immune microenvironment, impacts outcome. The goal of this study was to compare the Tumor Microenvironment (TME) of TNBC in the two mentioned groups in order to seek molecular parameters that are different in TNBC in AA patients as compared to whites. Methods: We selected N=50 AA and N=50 white TNBC samples from the Yale Pathology archives that were matched by diagnosis date. We measured CD45, CD3, CD8, CD20, CD14, CD68, PD-L1, THY1, aSMA and Fibroblast Activation Protein (FAP) expression in both the tumor and stromal compartments in whole slides from formalin fixed paraffin embedded (FFPE) tissues using multiplexed quantitative immunofluorescence (QIF). We also assessed the activation status of CD3-positive cells using Ki67 and Granzyme B markers. Median of each marker expression was calculated for each case by using quantitation from all Fields of View (FOV) that contained at least 10% tumor area. Results: AA tumors contained a significantly higher CD45-positive cells in overall, within tumor and stromal compartments (p = 0.0102, 0.0007 and 0.0280 respectively). Being more specific about CD45 marker, AA also showed to have a significantly higher level of overall lymphocyte population, measured by quantitating CD45+ CD14- cells (p =0.0081). AA tumors also had a significantly higher level of CD8 expression (p <0.0001). Even though we could not find any differences in CD3 expressions between the two groups, AA tumors contained a significantly higher level of activated T-cells (p =0.0432), where activation is defined as CD3 cells with high Ki67 or Granzyme B. AA tumors contained a significantly higher level of CD68 positive cells (p < 0.0001) and PD-L1 expression in CD68+ cells (p =0.0101). All other markers showed no difference between the two groups. Conclusion: Significant differences are seen in the TME of AA vs. white TNBCs. Further characterization of macrophages, fibroblasts, regulatory T-cells and Extracellular Matrix are underway to more specifically define TME and determine the relationship between TME features and outcome. Citation Format: Vesal Yaghoobi, Vasiliki Pelekanou, Tess O'Meara, Andrea Silber, Lajos Pusztai, David Rimm, Kim Blenman. Comparison of tumor immune microenvironment in triple negative breast cancer (TNBC) of African American versus that of white patients [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4973.