Human tumor-associated macrophage and monocyte transcriptional landscapes reveal cancer-specific reprogramming, biomarkers and therapeutic targets

Luca Cassetta, Stamatina Fragkogianni, Andrew H. Sims, Agnieszka Swierczak, Lesley M. Forrester, Hui Zhang, Daniel Soong, Tiziana Cotechini, Pavana Anur, Elaine Lin, Antonella Fidanza, Martha Lopez Yrigoyen, Michael Millar, Alexandra Urman, Zhichao Ai, Paul T. Spellman, E. Shelley Hwang, J Michael Dixon, Lisa Wiechmann, Lisa M CoussensHarriet W. Smith, Jeffrey W. Pollard

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)588-602.e10
Number of pages25
JournalCancer Cell
Volume35
Issue number4
Early online date28 Mar 2019
DOIs
Publication statusPublished - 15 Apr 2019

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