Grover Amit, Sanseviero Emilio, Timosenko Elina, Gabrilovich Dmitry I
AstraZeneca, ICC, Early Oncology, R&D, Cambridge, United Kingdom.
AstraZeneca, ICC, Early Oncology R&D, Gaithersburg, Maryland.
Cancer Discov. 2021 Nov;11(11):2693-2706. doi: 10.1158/2159-8290.CD-21-0764. Epub 2021 Oct 11.
Myeloid-derived suppressor cells (MDSC) are important regulators of immune responses in cancer. They represent a relatively stable form of pathologic activation of neutrophils and monocytes and are characterized by distinct transcriptional, biochemical, functional, and phenotypical features. The close association of MDSCs with clinical outcomes in cancer suggests that these cells can be an attractive target for therapeutic intervention. However, the complex nature of MDSC biology represents a substantial challenge for the development of selective therapies. Here, we discuss the mechanisms regulating MDSC development and fate and recent research advances that have demonstrated opportunities for therapeutic regulation of these cells. SIGNIFICANCE: MDSCs are attractive therapeutic targets because of their close association with negative clinical outcomes in cancer and established biology as potent immunosuppressive cells. However, the complex nature of MDSC biology presents a substantial challenge for therapeutic targeting. In this review, we discuss those challenges and possible solutions.
髓源性抑制细胞(MDSC)是癌症免疫反应的重要调节因子。它们代表了中性粒细胞和单核细胞病理激活的一种相对稳定形式,其特征在于独特的转录、生化、功能和表型特征。MDSC与癌症临床结果的密切关联表明,这些细胞可能是治疗干预的一个有吸引力的靶点。然而,MDSC生物学的复杂性对选择性疗法的开发构成了重大挑战。在这里,我们讨论调节MDSC发育和命运的机制以及最近的研究进展,这些进展已证明对这些细胞进行治疗调节的机会。意义:MDSC因其与癌症负面临床结果的密切关联以及作为强效免疫抑制细胞的既定生物学特性而成为有吸引力的治疗靶点。然而,MDSC生物学的复杂性对治疗靶向构成了重大挑战。在本综述中,我们讨论了这些挑战和可能的解决方案。