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:Myeloid-derived suppressor cells in cancer and cancer therapy.
Myeloid-derived suppressor cells in cancer and cancer therapy.
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抗癌药物继续在新获批药物清单中占据主导地位,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,免疫系统复杂且动态,既可产生抑瘤效应,也可产生促瘤效应。全面了解癌症中的免疫调节对于确定更有效的治疗策略至关重要。髓源性抑制细胞(MDSCs)是一群异质性髓系细胞,其发生与慢性炎症相关,而慢性炎症是癌症的一个标志。事实上,MDSCs 在肿瘤微环境中积聚,在其中强烈抑制 T 细胞和NK 细胞的抗癌功能,并发挥多种其他促瘤效应。新出现的证据表明,MDSCs 还导致对癌症治疗尤其是免疫治疗的耐药。相反,旨在消除癌细胞的治疗方法可对 MDSC 功能产生重要的额外影响,这些影响既可能是正面的,也可能是负面的。在本综述中,我们讨论 MDSCs 与肿瘤中发现的多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 MDSCs 与癌症治疗的相关性及其意义。
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.
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