Single-Cell Map of Diverse Immune Phenotypes in the Breast Tumor Microenvironment

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2018 Jul 3

PMID 29961579

Citations 1007

Authors

Elham Azizi

Ambrose J Carr

George Plitas

Andrew E Cornish

Catherine Konopacki

Sandhya Prabhakaran

Juozas Nainys

Kenmin Wu

Vaidotas Kiseliovas

Manu Setty

Kristy Choi

Rachel M Fromme

Phuong Dao

Peter T McKenney

Ruby C Wasti

Krishna Kadaveru

Linas Mazutis

Alexander Y Rudensky

Dana Peer

Affiliations

Soon will be listed here.

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.

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