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

By Luca Cassetta, Stamatina Fragkogianni, A. Sims, Agnieszka Swierczak, L. Forrester, Hui Zhang, D. Soong, T. Cotechini, Pavana Anur, Elaine Lin and 12 more. Cancer Cell, 2019

774 citations recorded by the source corpus.

Summary 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.

Subfields: Immunology, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/48fc6739d7baa8dcbedd4cc4c73b108d5c0e6885

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In Immunology

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In Molecular Biology

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In Oncology

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Citations in the corpus

• Inflammation and Cancer: Triggers, Mechanisms and Consequences (2019, background): “Tumor cell derived factors, such as TGFβ, other cytokines, metabolic cues or products of dead cells polarize local macrophages or incoming monocytes toward more “tissue repair” type, characterized by enhanced expression of tissue protective factors, growth factors and decreased expression of genes i”