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Cell ; 174(5): 1293-1308.e36, 2018 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-29961579

RESUMO

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.


Assuntos
Neoplasias da Mama/imunologia , Regulação Neoplásica da Expressão Gênica , Receptores de Antígenos de Linfócitos T/metabolismo , Análise de Sequência de RNA , Análise de Célula Única , Microambiente Tumoral/imunologia , Teorema de Bayes , Neoplasias da Mama/patologia , Análise por Conglomerados , Biologia Computacional , Feminino , Perfilação da Expressão Gênica , Humanos , Sistema Imunitário , Imunoterapia/métodos , Linfonodos , Linfócitos do Interstício Tumoral , Macrófagos/metabolismo , Fenótipo , Transcriptoma
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