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:Interleukin-6 (IL-6)-associated tumor microenvironment remodelling and cancer immunotherapy.
Interleukin-6 (IL-6)-associated tumor microenvironment remodelling and cancer immunotherapy.
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白细胞介素-6(IL-6)是一种促炎细胞因子,在炎症和免疫反应中发挥关键作用。近年来,IL-6在肿瘤微环境(TME)中影响肿瘤发生和免疫治疗应答的功能已被研究。基因突变主要负责癌症的发生发展,而TME中的相互作用也很重要,涉及癌细胞和非癌细胞。IL-6在这些相互作用中发挥重要作用,通过炎症通路增强肿瘤细胞的增殖、存活和转移,凸显其致癌功能。多种免疫细胞,包括巨噬细胞、T细胞、髓源性抑制细胞、树突状细胞和NK 细胞,均可受到IL-6的影响,从而形成免疫抑制性TME。IL-6还可通过增加PD-L1水平参与免疫逃逸,削弱治疗药物的疗效。值得注意的是,IL-6发挥双刃剑功能,既可增强也可减弱癌症免疫治疗,这为在癌症治疗中靶向该细胞因子带来了挑战。强调IL-6在TME中的复杂功能,有助于开发有效的癌症免疫治疗药物。
Interleukin-6 (IL-6) is a pro-inflammatory cytokine playing a pivotal role during inflammation and immune responses. In the recent years, the function of IL-6 in the tumor microenvironment (TME) for affecting tumorigenesis and immunotherapy response has been investigated. The genetic mutations are mainly responsible for the development of cancer, while interactions in TME are also important, involving both cancers and non-cancerous cells.
IL-6 plays a significant role in these interactions, enhancing the proliferation, survival and metastasis of tumor cells through inflammatory pathways, highlighting its carcinogenic function. Multiple immune cells including macrophages, T cells, myeloid-derived suppressor cells, dendritic cells and natural killer cells can be affected by IL-6 to develop immunosuppressive TME. IL-6 can also participate in the immune evasion through increasing levels of PD-L1, compromising the efficacy of therapeutics.
Notably, IL-6 exerts a double-edge sword function and it can dually increase or decrease cancer immunotherapy, providing a challenge for targeting this cytokine in cancer therapy. Highlighting the complicated function of IL-6 in TME can lead to the development of effective therapeutics for cancer immunity.
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