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Single-Cell Map of Diverse Immune Phenotypes in the Breast Tumor Microenvironment. - Published on 21 08 2018
2018 Jun 25. pii: S0092-8674(18)30723-2. doi: 10.1016/j.cell.2018.05.060.

Azizi E1, Carr AJ2, Plitas G3, Cornish AE1, Konopacki C4, Prabhakaran S1, Nainys J5, Wu K6, Kiseliovas V7, Setty M1, Choi K8, Fromme RM9, Dao P1, McKenney PT10, Wasti RC11, Kadaveru K11, Mazutis L1, Rudensky AY12, Pe'er D13.

Abstract

Knowledge of immune cell phenotypes in the tumor microenvironment is essential for understanding mechanisms of cancerprogression 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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This French program is organized by ITMO Cancer, in collaboration with ITMO BCDE (Cell Biology, Development and Evolution) and ITMO Technologies for Health of the National Alliance for Life Sciences and Health (AVIESAN) with the National Cancer Institute (INCA) and Inserm within the framework of the Cancer Plan. Operational management is entrusted to Inserm.
It was launch in order to develop a critical mass of resources and skills in order to conduct interdisciplinary research projects in the field of functional heterogeneity of cellular tumor relations in their ecosystem: the "HTE Program".

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