Single-Cell Map of Diverse Immune Phenotypes in the Breast Tumor Microenvironment
Menée à l'aide de 45 000 cellules immunitaires issues d'échantillons de tissu tumoral, de tissu sain, de sang et de ganglions lymphatiques prélevés sur 8 patientes atteintes d'un carcinome du sein, puis à l'aide de 27 000 lymphocytes T complémentaires, cette étude analyse la diversité des phénotypes de lymphocytes T dans le micro-environnement tumoral, puis suggère un modèle rendant compte de cette diversité
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.
Cell , résumé, 2017