Abstract 2729: Cell infiltration prediction of breast cancer tissues identifies basophils as potentially important immune cells in the tumor microenvironment
Authors: Garai Jone , Dutil Julie , Cress Douglas W. , Seewaldt Victoria , Teer Jamie K. , Fejerman Laura , Miele Lucio , Zabaleta Jovanny 
Published: July 2021

Abstract
Background: Breast cancer (BC) is the most common and deadliest cancer in women worldwide. Hormone receptor (HR) positive tumors (luminal) are the most frequent while HER-2 overexpressing (HR-, HER2+) and triple negative (TNBC, HR-/HER2-) are most deadly. HR+ subtypes are more common in non-Hispanic White women while HER-2 and TNBC present either higher prevalence or risk of mortality in minority groups. Hispanic/Latinos (H/L) is the largest and fastest growing minority in the U.S.A. However, H/L women have been underrepresented in BC studies. We reported that luminal B is the most common BC subtype in a group of H/L and that ERBB2, GRB7 and MIEN1 genes have increased expression in women with higher Indigenous American ancestry. Immune infiltration of tumors has become a hallmark for the prediction of outcome. However, contrary to TNBC, luminal tumors have been considered low immunogenic. Immune infiltration of luminal B tumors in H/L has not yet been investigated. Our goal was to predict immune infiltration of luminal B tumors based on RNA-seq data and according to the levels of body mass index (BMI) and ancestral fractions (West African, European, Indigenous American).
Methods: We performed RNA-seq in 70 luminal B tumors of H/L from Puerto Rico. Ancestry was estimated by genotyping on the Affymetrix U.K. Biobank array and global ancestry proportions determined with Admixture Software v1.3, using 1000 Genomes reference population for anchoring. BMI, age at diagnosis and tumor size were extracted from the Electronic Medical Records. We used Partek Flow for the RNA-seq analysis based on ancestry fraction and BMI. Prediction of cell populations was done in xCell. Correlation analysis was done in GraphPad Prism v7.05.
Results: We found an inverse correlation between Indigenous American and γδ-T cell infiltration (R2= -0.3; p=0.03) while BMI was associated with increased infiltration of basophils (R2=0.3; p=0.026). Among women with high BMI, those with low European ancestry had increased levels of basophils infiltration R2=0.66; p=0.17) and those with high European ancestry had reduced infiltration of naïve CD8+ T cells (R2= -0.53; p=0.008) and reduced plasmacytoid dendritic cells (pDC, R2=-0.51; p=0.01).
Conclusions: We found that luminal B tumors have infiltration of immune cells that may contribute to differences in the response to treatment and outcome. To the best of our knowledge, the role of infiltrating basophils into breast cancer tissues has not been described. However, circulating basophils and predicted infiltration of basophils into ovarian and colorectal cancer tissues have been correlated with survival. Our findings have to be confirmed in a larger set of samples and by additional methods, including immunohistochemistry.
Citation Format: Jone Garai, Julie Dutil, Douglas W. Cress, Victoria Seewaldt, Jamie K. Teer, Laura Fejerman, Lucio Miele, Jovanny Zabaleta. Cell infiltration prediction of breast cancer tissues identifies basophils as potentially important immune cells in the tumor microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2729.