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

By E. Azizi, Ambrose J. Carr, G. Plitas, A. Cornish, Catherine Konopacki, Sandhya Prabhakaran, J. Nainys, Kenmin Wu, V. Kiseliovas, Manu N. Setty and 9 more. Cell, 2018

1,709 citations recorded by the source corpus.

SUMMARY 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 node, 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, with important implications for characterizing tumor-infiltrating immune cells.

Subfields: Immunology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/5a3211ad5187f60087a323779c629b778728e60c

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Citations in the corpus

Dysfunctional CD8+ T cells form a proliferative, dynamically regulated compartment within human melanoma (2018, positive): “In line with previous observations (Azizi et al., 2018; Guo et al., 2018), our data show that the dysfunctional T cell pool does not form a discrete cell population but is part of a wide differentiation spectrum, spanning from transitional through early dysfunctional toward highly dysfunctional T ce”
Spatiotemporal analysis of human intestinal development at single-cell resolution (2021, positive): “, 2017), and the second expressed genes involved in complement formation (C1QA, C1QC) and IL1B at a higher level – in keepingwith a classically activated (M1) phenotype (Azizi et al., 2018; Zhang et al., 2020).”
Identifying phenotype-associated subpopulations by integrating bulk and single-cell sequencing data (2021, neutral): “9).”
Organoid modeling of the tumor immune microenvironment (2018, background): “Recent paired single-cell TCR and transcriptome measurements have also found breast cancer clonotype phenotypes (Azizi et al., 2018).”
Single-cell analysis reveals fibroblast clusters linked to immunotherapy resistance in cancer. (2020, background): “21 these studies being focused on immune cell heterogeneity (31,45-51).”
Single-Cell Profiling and SCOPE-Seq Reveal Lineage Dynamics of Adult Ventricular-Subventricular Zone Neurogenesis and NOTUM as a Key Regulator (2020, positive): “To test this, we calculated the phenotypic volume of each cluster in the trajectory, a metric for cellular heterogeneity (Azizi et al., 2018).”