We created a comprehensive atlas of breast tumor-immune ecosystem by collecting a dataset of over 50,000 single immune cell transcriptomes from different types of human breast cancer, normal breast tissue, peripheral blood, and the lymph node using single-cell RNA-seq, and analyzed with novel computational clustering and normalization techniques. Our analyses revealed remarkably increased heterogeneity of intratumoral cells of both lymphoid and myeloid cell lineages, which occupy significantly expanded contiguous phenotypic space in comparison to normal breast tissue. The observed continuum of cell states is associated with their progressive cellular activation and differentiation and argues strongly against the notion of few discrete states of differentiation or activation of individual cell types shaping the tumor microenvironment. The substantial heterogeneity of cell states within major cell types and across patients is also driven by complex coexpression relationships between genes, and by extension their potential suitability as therapeutic cotargets.

Citation Format: Dana Pe’er. An atlas of the tumor immune ecosystem [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2017 Oct 1-4; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2018;6(9 Suppl):Abstract nr IA14.