Single-Cell Map of Diverse Immune Phenotypes in the Breast Tumor Microenvironment
Single-Cell Map of Diverse Immune Phenotypes in the Breast Tumor Microenvironment
Abstract
Knowledge of immune cell phenotypes in the tumor microenvironment is essential for understanding mechanisms of cancer progression and immunotherapy response. We profiled 45,000 immune cells from eight breast carcinomas, as well as matched normal breast tissue, blood, and lymph nodes, using single-cell RNA-seq. We developed a preprocessing pipeline, SEQC, and a Bayesian clustering and normalization method, Biscuit, to address computational challenges inherent to single-cell data. Despite significant similarity between normal and tumor tissue-resident immune cells, we observed continuous phenotypic expansions specific to the tumor microenvironment. Analysis of paired single-cell RNA and T cell receptor (TCR) sequencing data from 27,000 additional T cells revealed the combinatorial impact of TCR utilization on phenotypic diversity. Our results support a model of continuous activation in T cells and do not comport with the macrophage polarization model in cancer. Our results have important implications for characterizing tumor-infiltrating immune cells.
Results
Figure1
Figure1 shows scRNA-seq basic data information .
Plot E indicates hallmark hypoxia signature scores, where the right side shows heatmap of Z-scored mean expression of genes in signature and the top side shows barplot of total expression of each gene, across all patients.
Figure2
Figure2 indicates characterization of immune of patients.
Figure3
Figure3 shows impact of the Microenvironment on Breast Immune Cells.
Figure4
Figure4 shows the detailed characterization of T cells.
Plot a shows the T cell’s trajectory.
Figure5
Figure5 shows the identification of Treg clusters through conariance patterns.