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  • Review Article
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Myeloid-derived suppressor cells in cancer and cancer therapy

Abstract

Anticancer agents continue to dominate the list of newly approved drugs, approximately half of which are immunotherapies. This trend illustrates the considerable promise of cancer treatments that modulate the immune system. However, the immune system is complex and dynamic, and can have both tumour-suppressive and tumour-promoting effects. Understanding the full range of immune modulation in cancer is crucial to identifying more effective treatment strategies. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of myeloid cells that develop in association with chronic inflammation, which is a hallmark of cancer. Indeed, MDSCs accumulate in the tumour microenvironment, where they strongly inhibit anticancer functions of T cells and natural killer cells and exert a variety of other tumour-promoting effects. Emerging evidence indicates that MDSCs also contribute to resistance to cancer treatments, particularly immunotherapies. Conversely, treatment approaches designed to eliminate cancer cells can have important additional effects on MDSC function, which can be either positive or negative. In this Review, we discuss the interplay between MDSCs and various other cell types found in tumours as well as the mechanisms by which MDSCs promote tumour progression. We also discuss the relevance and implications of MDSCs for cancer therapy.

Key points

  • Cancer-associated conditions, including hypoxia, nutrient deficiency, acidity, endoplasmic reticulum stress and long-term production of inflammatory mediators, promote the generation of myeloid-derived suppressor cells (MDSCs).

  • MDSCs support the progression of most cancer entities by suppressing antitumour immune responses, stimulating angiogenesis and fostering metastasis through a variety of mechanisms.

  • MDSCs contribute to primary and acquired resistance to cancer immunotherapy; thus, combinatorial therapeutic targeting of these cells might improve patient outcomes.

  • Other cancer treatments, such as chemotherapy, radiotherapy, targeted therapies or hormone therapies, can have distinct and disparate effects on MDSCs and should be studied further.

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Fig. 1: The nurturing relationship between MDSCs and tumours.
Fig. 2: Implications of MDSCs for cancer therapy.

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Lasser, S.A., Ozbay Kurt, F.G., Arkhypov, I. et al. Myeloid-derived suppressor cells in cancer and cancer therapy. Nat Rev Clin Oncol 21, 147–164 (2024). https://doi.org/10.1038/s41571-023-00846-y

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