Journal
NATURE REVIEWS DRUG DISCOVERY
Volume 17, Issue 12, Pages 887-904Publisher
NATURE PORTFOLIO
DOI: 10.1038/nrd.2018.169
Keywords
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Funding
- Wellcome Trust [101067/Z/13/Z]
- Medical Research Council (MRC) Centre [MR/N022556/1]
- MRC [MR/N022556/1] Funding Source: UKRI
- Wellcome Trust [101067/Z/13/Z] Funding Source: Wellcome Trust
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Infiltration of macrophages in solid tumours is associated with poor prognosis and correlates with chemotherapy resistance in most cancers. In mouse models of cancer, macrophages promote cancer initiation and malignant progression by stimulating angiogenesis, increasing tumour cell migration, invasion and intravasation and suppressing antitumour immunity. At metastatic sites, macrophages promote tumour cell extravasation, survival and subsequent growth. Each of these pro-tumoural activities is promoted by a subpopulation of macrophages that express canonical markers but have unique transcriptional profiles, which makes tumour-associated macrophages (TAMs) good targets for anticancer therapy in humans through either their ablation or their re-differentiation away from pro-tumoural towards antitumoural states. In this Review, we evaluate the state of the art of TAM-targeting strategies, focusing on the limitations and potential side effects of the different therapies such as toxicity, rebound effects and compensatory mechanisms. We provide an extensive overview of the different types of therapy used in the clinic and their limitations in light of known macrophage biology and propose new strategies for targeting TAMs.
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