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Targeting macrophages: therapeutic approaches in cancer

Abstract

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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Figure 1: Macrophage infiltration and survival in cancer.
Figure 2: Macrophage diversity drives tumour progression to metastasis and resistance to therapy.
Figure 3: Targeting and reprogramming TAM pro-tumoural activities.
Figure 4: Selective examples of anti-TAM drugs currently under clinical trial investigation.

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Acknowledgements

The authors apologize to the many authors whose work they could not cite owing to space constraints. Research in the authors' laboratories is supported by the Wellcome Trust (101067/Z/13/Z) and Medical Research Council (MRC) Centre grant MR/N022556/1 to J.W.P.

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Correspondence to Jeffrey W. Pollard.

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Cassetta, L., Pollard, J. Targeting macrophages: therapeutic approaches in cancer. Nat Rev Drug Discov 17, 887–904 (2018). https://doi.org/10.1038/nrd.2018.169

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