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:Transforming Growth Factor-β1 in Cancer Immunology: Opportunities for Immunotherapy.
Transforming Growth Factor-β1 in Cancer Immunology: Opportunities for Immunotherapy.
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转化生长因子-β1(TGF-β)以情境依赖的方式调控大量细胞内在过程,从而调节肿瘤进展。因此,尽管TGF-β在肿瘤发生的早期阶段作为肿瘤抑制因子发挥作用,但在晚期阶段,该因子促进肿瘤进展和转移。此外,TGF-β还通过调节免疫系统影响肿瘤微环境。在这方面,TGF-β表现出强效的免疫抑制作用,使癌细胞能够逃避免疫监视,并赋予对免疫治疗的耐药性。TGF-β抑制T细胞淋巴细胞、树突状细胞和NK 细胞的活化及抗肿瘤功能,同时促进T调节细胞和髓源性抑制细胞的生成,这些细胞阻碍抗肿瘤T细胞活性。此外,TGF-β促进肿瘤相关巨噬细胞和中性粒细胞分别从M1向M2和从N1向N2极化。总之,这些效应有助于形成免疫抑制性肿瘤微环境并支持肿瘤促进。本综述旨在分析TGF-β在肿瘤免疫学中复杂作用的相关证据、联合免疫治疗的当前结局,以及可能提高当前和新型肿瘤治疗成功率的抗TGF-β疗法。
Transforming growth factor-beta1 (TGF-β) regulates a plethora of cell-intrinsic processes that modulate tumor progression in a context-dependent manner.
Thus, although TGF-β acts as a tumor suppressor in the early stages of tumorigenesis, in late stages, this factor promotes tumor progression and metastasis.
In addition, TGF-β also impinges on the tumor microenvironment by modulating the immune system. In this aspect, TGF-β exhibits a potent immunosuppressive effect, which allows both cancer cells to escape from immune surveillance and confers resistance to immunotherapy. While TGF-β inhibits the activation and antitumoral functions of T-cell lymphocytes, dendritic cells, and natural killer cells, it promotes the generation of T-regulatory cells and myeloid-derived suppressor cells, which hinder antitumoral T-cell activities.
Moreover, TGF-β promotes tumor-associated macrophages and neutrophils polarization from M1 into M2 and N1 to N2, respectively. Altogether, these effects contribute to the generation of an immunosuppressive tumor microenvironment and support tumor promotion. This review aims to analyze the relevant evidence on the complex role of TGF-β in cancer immunology, the current outcomes of combined immunotherapies, and the anti-TGF-β therapies that may improve the success of current and new oncotherapies.
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