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:The (Sialyl) Tn antigen: Contributions to immunosuppression in gastrointestinal cancers.
The (Sialyl) Tn antigen: Contributions to immunosuppression in gastrointestinal cancers.
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细胞信号通路受到精细调控以维持稳态。在癌症进展过程中,这些机制被操控而变得有害。O-糖基化是一种关键的翻译后修饰,就是这样一种通路,可导致糖蛋白产生多种异构体。由于蛋白质上完全分支的O-聚糖链合成不完全而产生的Tn(GalNAc-O-Ser/Thr)和Sialyl Tn(STn;Neu5Ac-GalNAc-O-Ser/Thr)抗原,促进了胰腺及其他胃肠道癌症的疾病进展。肿瘤微环境(TME)是肿瘤的主要组成部分,也是其行为的关键调节因素。TME的多种细胞和分泌成分决定了肿瘤的发展和转移。巨噬细胞、自然杀伤(NK)细胞、树突状细胞、B和T淋巴细胞等免疫细胞是肿瘤“免疫”微环境(TIME)的一部分。已发现肿瘤上Tn和STn抗原的表达可调节这些免疫细胞的功能,并改变其正常的抗肿瘤细胞毒性作用。这可以通过多种细胞内在和外在信号通路实现,本综述对此进行了阐述。研究Tn/STn抗原与胃肠道癌症TIME之间的相互作用,有助于开发更好、更稳健的疗法,以抵消免疫抑制机制,使这些肿瘤对抗癌治疗敏感。
Cellular signaling pathways are intricately regulated to maintain homeostasis. During cancer progression, these mechanisms are manipulated to become harmful. O-glycosylation, a crucial post-translational modification, is one such pathway that can lead to multiple isoforms of glycoproteins. The Tn (GalNAc-O-Ser/Thr) and Sialyl Tn (STn; Neu5Ac-GalNAc-O-Ser/Thr) antigens resulting from the incomplete synthesis of fully branched O-glycan chains on proteins contribute to disease progression in the pancreas and other gastrointestinal cancers. The tumor microenvironment (TME) is a major constituent of tumors and a key modulator of their behavior. Multiple cellular and secretory components of the TME dictate the development and metastasis of tumors.
Immune cells like macrophages, natural killer (NK) cells, dendritic cells, B and T lymphocytes are a part of the tumor "immune" microenvironment (TIME). The expression of the Tn and STn antigens on tumors has been found to regulate the function of these immune cells and alter their normal antitumor cytotoxic role.
This is possible through multiple cell intrinsic and extrinsic signaling pathways, elaborated in this review. Studying the interaction between Tn/STn antigens and the TIME of gastrointestinal cancers can help develop better and more robust therapies that can counteract immunosuppressive mechanisms to sensitize these tumors to anticancer therapies.
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