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Human Tumor-Associated Macrophage and Monocyte Transcriptional Landscapes Reveal Cancer-Specific Reprogramming, Biomarkers, and Therapeutic Targets.

TitleHuman Tumor-Associated Macrophage and Monocyte Transcriptional Landscapes Reveal Cancer-Specific Reprogramming, Biomarkers, and Therapeutic Targets.
Publication TypeJournal Article
Year of Publication2019
AuthorsCassetta L, Fragkogianni S, Sims AH, Swierczak A, Forrester LM, Zhang H, Soong DYH, Cotechini T, Anur P, Lin EY, Fidanza A, Lopez-Yrigoyen M, Millar MR, Urman A, Ai Z, Spellman PT, E Hwang S, J Dixon M, Wiechmann L, Coussens LM, Smith HO, Pollard JW
JournalCancer Cell
Date Published2019 Mar 12
ISSN1878-3686
Abstract

The roles of tumor-associated macrophages (TAMs) and circulating monocytes in human cancer are poorly understood. Here, we show that monocyte subpopulation distribution and transcriptomes are significantly altered by the presence of endometrial and breast cancer. Furthermore, TAMs from endometrial and breast cancers are transcriptionally distinct from monocytes and their respective tissue-resident macrophages. We identified a breast TAM signature that is highly enriched in aggressive breast cancer subtypes and associated with shorter disease-specific survival. We also identified an auto-regulatory loop between TAMs and cancer cells driven by tumor necrosis factor alpha involving SIGLEC1 and CCL8, which is self-reinforcing through the production of CSF1. Together these data provide direct evidence that monocyte and macrophage transcriptional landscapes are perturbed by cancer, reflecting patient outcomes.

DOI10.1016/j.ccell.2019.02.009
Alternate JournalCancer Cell
PubMed ID30930117
Publication institute
CRM