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 double-edged role of interferon gamma in cancer immunity.
The double-edged role of interferon gamma in cancer immunity.
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干扰素-γ(IFN-γ)是一种关键细胞因子,协调针对病毒和胞内病原体感染的免疫应答。缺乏IFN-γ的敲除(KO)小鼠表现出细胞毒性T淋巴细胞(CTLs)和自然杀伤(NK)细胞消除肿瘤细胞的能力显著降低,导致肿瘤生长和转移加速。这些发现强调了IFN-γ在调控抗肿瘤免疫应答中的关键作用。然而,许多晚期肿瘤表现出IFN-γ信号失调,这发挥直接的促肿瘤和免疫抑制效应,从而使癌细胞逃避免疫监视并促进癌症进展。IFN-γ在调控癌症免疫中的这种双重作用限制了其在癌症中的治疗应用。理解IFN-γ发挥抗肿瘤或促肿瘤作用的具体条件,是优化其在癌症治疗中应用的一项挑战。
Interferon-gamma (IFN-γ) is a pivotal cytokine that coordinates the immune response to infections caused by viruses and intracellular pathogens. Knockout (KO) mice lacking IFN-γ exhibited a significant reduction in the capacity of cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells to eliminate tumor cells, resulting in accelerated tumor growth and metastasis.
These findings underscore the key role of IFN-γ in regulating the antitumor immune response.
However, many advanced tumors exhibit dysregulated IFN-γ signaling, which exerts direct protumoral and immunosuppressive effects, thereby allowing cancer cells to evade immune surveillance and promoting cancer progression. This dual role of IFN-γ in regulating cancer immunity has limited its therapeutic use in cancer. Understanding the specific conditions under which IFN-γ has an antitumoral or a protumoral role is a challenge for optimizing its use in cancer therapy.
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