RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Targeting myeloid-derived suppressor cells in tumor immunotherapy: Current, future and beyond.
Targeting myeloid-derived suppressor cells in tumor immunotherapy: Current, future and beyond.
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髓源性抑制细胞(MDSCs)因其强大的免疫抑制能力,是肿瘤微环境(TME)中主要的负性调控因子之一。MDSCs是骨髓中髓系祖细胞异常分化的产物,其抑制T细胞、NK 细胞和树突状细胞介导的免疫应答;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;最终导致肿瘤进展和转移。在这篇综述中,我们重点介绍TME中MDSCs生物学的关键特征,这些特征正被探索作为肿瘤免疫治疗的潜在靶点。我们讨论旨在将TME从免疫抑制状态重编程为免疫刺激状态的治疗和策略,这些策略可阻止MDSC的免疫抑制活性;促进MDSC分化;并影响MDSC在肿瘤部位的募集和丰度。我们还总结了在识别合理的联合策略以提高癌症患者临床疗效和预后方面的最新进展,这些进展得益于深入理解和探究TME中MDSCs产生和抑制的机制及特征。
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, via deeply understanding and pursuing the mechanisms and characterization of MDSCs generation and suppression in TME.
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