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靶向肿瘤免疫治疗中的髓源抑制细胞:当前、未来及以后。

Targeting myeloid-derived suppressor cells in tumor immunotherapy: Current, future and beyond.

机构信息

State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.

Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China.

出版信息

Front Immunol. 2023 Mar 17;14:1157537. doi: 10.3389/fimmu.2023.1157537. eCollection 2023.

Abstract

Myeloid-derived suppressor cells (MDSCs) are one of the major negative regulators in tumor microenvironment (TME) due to their potent immunosuppressive capacity. MDSCs are the products of myeloid progenitor abnormal differentiation in bone marrow, which inhibits the immune response mediated by T cells, natural killer cells and dendritic cells; promotes the generation of regulatory T cells and tumor-associated macrophages; drives the immune escape; and finally leads to tumor progression and metastasis. In this review, we highlight key features of MDSCs biology in TME that are being explored as potential targets for tumor immunotherapy. We discuss the therapies and approaches that aim to reprogram TME from immunosuppressive to immunostimulatory circumstance, which prevents MDSC immunosuppression activity; promotes MDSC differentiation; and impacts MDSC recruitment and abundance in tumor site. We also summarize current advances in the identification of rational combinatorial strategies to improve clinical efficacy and outcomes of cancer patients, deeply understanding and pursuing the mechanisms and characterization of MDSCs generation and suppression in TME.

摘要

髓源性抑制细胞(MDSCs)是肿瘤微环境(TME)中主要的负调控因子之一,因其具有强大的免疫抑制能力。MDSCs 是骨髓中髓样前体异常分化的产物,可抑制 T 细胞、自然杀伤细胞和树突状细胞介导的免疫反应;促进调节性 T 细胞和肿瘤相关巨噬细胞的生成;驱动免疫逃逸;最终导致肿瘤的进展和转移。在这篇综述中,我们强调了 MDSCs 在 TME 中的生物学特性,这些特性正在被探索作为肿瘤免疫治疗的潜在靶点。我们讨论了旨在将 TME 从免疫抑制转变为免疫刺激环境的治疗方法和策略,这些策略可以防止 MDSC 的免疫抑制活性;促进 MDSC 的分化;并影响肿瘤部位 MDSC 的募集和丰度。我们还总结了目前在确定合理的联合策略方面的进展,以提高癌症患者的临床疗效和结果,深入了解和探索 MDSCs 在 TME 中的产生和抑制的机制和特征。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/288b/10063857/8161026581cd/fimmu-14-1157537-g001.jpg

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