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:Orchestration of immune response by innate lymphoid cell subtype 2 at various tumor microenvironment, a suitable target for cancer immunotherapy.
Orchestration of immune response by innate lymphoid cell subtype 2 at various tumor microenvironment, a suitable target for cancer immunotherapy.
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固有淋巴样细胞是一个混合细胞群体,也是我们固有免疫系统的重要调节者。根据近期科学文献,组织驻留固有淋巴样细胞亚型2已被认为是2型炎症反应的重要参与者,参与胰腺癌、肺癌、急性髓系白血病、胃肠道肿瘤等多种人类恶性肿瘤。目前的报道揭示,在三种主要ILC亚型中,亚型2(ILC 2)是肿瘤微环境(TME)中启动2型炎症反应的关键调节者。ILC-2的这种激活是ILC-2发挥特定下游功能非常重要的一步。ILC-2经不同趋化因子致敏后,会从活化的ILC-2中分泌不同的细胞因子,如IL-4、IL-5、IL-13、IL-9,这些细胞因子诱导2型炎症反应,并参与与其他免疫细胞如NK细胞、细胞毒性T细胞、MDSC和T reg细胞的复杂相互作用。在初始阶段,ILC-2通过IL-33激活可能诱导由ILC-2/嗜酸性粒细胞轴介导的抗肿瘤效应。
然而,也有证据表明,PDG2(前列腺素D2)介导的ILC-2激活会在TME中诱导ILC-2/MDSC免疫抑制性促肿瘤生态位。在本综述中,我们基于近期科学工作总结了ILC-2在癌症免疫中的作用,这些工作表明ILC-2发挥双重作用,并在不同癌症环境中协调免疫反应向2型免疫偏移。癌症是一种复杂疾病,其中身体细胞的异常生长破坏了受累身体组织的正常功能。它也是全球各大洲的主要死亡原因之一。迄今为止,已发现100多种人类癌症。
我们的身体拥有免疫系统,它始终在对抗包括癌细胞在内的任何有害因子,癌细胞试图侵入我们的免疫系统并使我们生病。我们的免疫系统由称为免疫细胞的不同特化细胞组成,这些细胞可能直接参与杀死癌细胞,也可能通过复杂的相互作用间接帮助其他细胞完成这一过程。先天淋巴细胞或ILC就是我们免疫系统中这类免疫细胞。先天淋巴细胞有三个主要亚型ILC-1、ILC-2、ILC-3;然而,在癌症发生和进展的背景下,近年来,ILC-2已被认为是关键参与者之一。
因此,在本文中,我们总结了ILC-2在不同癌症环境中的激活和各种功能,结论是ILC-2可以是一个相当好的治疗靶点,用于对抗称为癌症的毁灭性疾病。
Innate lymphoid cells are a mixed population of cells and critical regulators of our innate immune system. According to recent scientific literature, tissue resident innate lymphoid cell subtype 2 has been recognized as an important player of type 2 inflammatory responses, involved in different human malignancies like pancreatic, lung, acute myeloid leukemia, gastrointestinal tract cancer, etc. The current reports have revealed that, among the three main ILC sub types, subtype 2 (ILC 2), as the key regulator of initiating the type 2 inflammatory responses at the tumor microenvironment (TME).
This activation of ILC-2 is a very important step for the specific downstream functioning of ILC-2. Priming of ILC-2 with different chemokines involves different cytokine secretion from the activated ILC-2 like IL-4, IL-5, IL-13, IL-9 which induce type 2 inflammatory responses involved in the complex interaction with other immune cells like NK cell, Cytotoxic T cell, MDSC and T reg cell. At the initial stage, ILC-2 activation through IL-33 may induce the anti-tumorigenic effect mediated by ILC-2/eosinophil axis.
However, it is also evident that PDG2 (Prostaglandin D2)-mediated activation of ILC-2 induces the ILC-2/MDSC immune suppressive pro-tumorigenic niche at the TME.
Here, in this review, we have summarized the function of ILC-2 on cancer immunity based on recent scientific work which indicates ILC-2 plays a dual role and orchestrates the immune responses toward type 2 immunity in different cancer settings. Cancer is a complex disease where abnormal growth of body cells destroys the normal functions of affected body tissue. It is also one of the leading causes of death worldwide across every continent. There are more than 100 human cancers have been identified until now.
Our body has an immune system, which always fights against any harmful agent including cancer cells, which try to invade our immune system and makes us fall ill.
Our immune system consists of different specialized cells termed as immune cells which may involve in the direct killing of the cancer cells or it may indirectly help other cells to do it via complex interactions. Innate lymphoid cell or ILC is such type of immune cells of our immune system. Innate lymphoid cell has three main subtypes ILC-1, ILC-2, ILC-3; however, in the context of cancer development and progression, recently, ILC-2 has been recognized as one of the key players.
Thus, in this article, we have summarized the activation and various functions of ILC-2 in different cancer settings which conclude that, ILC-2 can be a reasonably good therapeutic target to combat the devastating disease called cancer.
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