Abstract 140: Comprehensive analysis of immune evasion in breast cancer by single-cell RNA-seq

Abstract

Abstract The tumor microenvironment is composed of numerous cell types, including tumor, immune and stromal cells. Cancer cells interact with the tumor microenvironment to suppress anticancer immunity. In this study, we molecularly dissected the tumor microenvironment of breast cancer by single-cell RNA-seq. The breast tumor microenvironment was profiled by analyzing the single-cell transcriptomes of 52,163 cells from the tumor tissues of 15 breast cancer patients. The tumor cells and immune cells from individual patients were analyzed simultaneously at the single-cell level. Among more than 40,000 tumor cells, we identified distinct cell clusters with different molecular subtypes and gene signatures in the same tumor, which revealed intra-tumor heterogeneity in breast cancer. We comprehensively profiled the functional state of T cells, macrophages, B cells, CAFs in breast cancer tumor microenvironment, which highlight the immune cell and CAF diversity in the breast cancer TME. Moreover, we analyzed intercellular communication in the breast cancer TME using a dataset of human ligand receptor pairs, which showed distinct cell interaction models across tumors. The evolution of the tumor microenvironment during clinical treatment was dissected by comparing tumor microenvironment of breast cancer pre- and post-chemotherapy. This study investigated the diversity of the cell types in the tumor microenvironment and provided information on the mechanisms of escape from clearance by immune cells in breast cancer, which could be a beneficial resource for immunotherapy development. Citation Format: Jianhua Yin, Hanlin Zhou, Chen Yan, Ruqian lv, Ting Wang, Chenyang He, Chen Huang, Yong Hou, Shida Zhu, Ling Wang, Michael Dean, Kui Wu, Hong Hu, Guibo Li. Comprehensive analysis of immune evasion in breast cancer by single-cell RNA-seq [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 140.