Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Heidelberg University, Mannheim, Germany.
Skin Cancer Unit, German Cancer Research Center (Deutsches Krebsforschungszentrum (DKFZ)), Heidelberg, Germany.
Nat Rev Clin Oncol. 2024 Feb;21(2):147-164. doi: 10.1038/s41571-023-00846-y. Epub 2024 Jan 8.
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.
抗癌药物继续主导新批准药物的清单,其中约一半是免疫疗法。这一趋势表明,调节免疫系统的癌症治疗具有相当大的前景。然而,免疫系统是复杂和动态的,它既可以抑制肿瘤,也可以促进肿瘤。了解癌症中免疫调节的全部范围对于确定更有效的治疗策略至关重要。髓系来源的抑制细胞(MDSCs)是一组异质性的髓样细胞,它们在慢性炎症中发育,而慢性炎症是癌症的一个标志。事实上,MDSCs 在肿瘤微环境中积累,在那里它们强烈抑制 T 细胞和自然杀伤细胞的抗癌功能,并发挥各种其他促进肿瘤的作用。新出现的证据表明,MDSCs 也有助于癌症治疗的耐药性,特别是免疫治疗。相反,旨在消除癌细胞的治疗方法可能对 MDSC 功能产生重要的额外影响,这些影响可能是积极的,也可能是消极的。在这篇综述中,我们讨论了 MDSCs 与肿瘤中发现的各种其他细胞类型之间的相互作用,以及 MDSCs 促进肿瘤进展的机制。我们还讨论了 MDSCs 对癌症治疗的相关性和意义。