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:Schisandrin C enhances type I IFN response activation to reduce tumor growth and sensitize chemotherapy through antitumor immunity.
Schisandrin C enhances type I IFN response activation to reduce tumor growth and sensitize chemotherapy through antitumor immunity.
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随着免疫学理解的不断深入,越来越多的免疫疗法正在癌症治疗领域被探索和应用。cGAS-STING通路作为先天免疫应答的关键组成部分,已被证实在癌症免疫治疗中具有关键作用。
我们在4T1和MC38荷瘤小鼠中评估了五味子木脂素成分五味子素C(SC)的抗肿瘤作用,并通过RNA测序、qRT-PCR和流式细胞术研究了SC对cGAS-STING通路和抗肿瘤免疫的增强作用。
我们的研究结果显示,SC在乳腺癌和结肠癌模型中均显著抑制肿瘤生长。这种肿瘤生长的抑制归因于I型IFN应答的激活以及肿瘤内T细胞和NK细胞数量的增加。
此外,SC显著促进了顺铂诱导的cGAS-STING通路激活。与顺铂单药治疗相比,SC与顺铂联合治疗对肿瘤生长表现出更强的抑制作用。化疗疗效的增强与I型IFN应答的增强和抗肿瘤免疫的强化相关。SC通过增强I型IFN应答激活和提升抗肿瘤免疫来减少肿瘤生长并提高化疗敏感性,这丰富了五味子抗肿瘤免疫的研究,并为其在对抗乳腺癌和结肠癌中的应用奠定了理论基础。
With the advancing comprehension of immunology, an increasing number of immunotherapies are being explored and implemented in the field of cancer treatment. The cGAS-STING pathway, a crucial element of the innate immune response, has been identified as pivotal in cancer immunotherapy.
We evaluated the antitumor effects of Schisandra chinensis lignan component Schisandrin C (SC) in 4T1 and MC38 tumor-bearing mice, and studied the enhancing effects of SC on the cGAS-STING pathway and antitumor immunity through RNA sequencing, qRT-PCR, and flow cytometry.
Our findings revealed that SC significantly inhibited tumor growth in models of both breast and colon cancer. This suppression of tumor growth was attributed to the activation of type I IFN response and the augmented presence of T cells and NK cells within the tumor.
Additionally, SC markedly promoted the cGAS-STING pathway activation induced by cisplatin. In comparison to cisplatin monotherapy, the combined treatment of SC and cisplatin exhibited a greater inhibitory effect on tumor growth. The amplified chemotherapeutic efficacy was associated with an enhanced type I IFN response and strengthened antitumor immunity.
SC was shown to reduce tumor growth and increase chemotherapy sensitivity by enhancing the type I IFN response activation and boosting antitumor immunity, which enriched the research into the antitumor immunity of S. chinensis and laid a theoretical basis for its application in combating breast and colon cancer.
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