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:Calf Thymus Polypeptide Restrains the Growth of Colorectal Tumor via Regulating the Intestinal Microbiota-Mediated Immune Function.
Calf Thymus Polypeptide Restrains the Growth of Colorectal Tumor via Regulating the Intestinal Microbiota-Mediated Immune Function.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
小牛胸腺多肽(CTP)分子量小于10 kDa,是从小于30日龄新生牛胸腺中制备的。本研究在B6/JGpt-Apc em1Cin(MinC)/Gpt(Apc Min/+)小鼠中研究了CTP对结直肠癌(CRC)的抑制作用。CTP抑制了Apc Min/+小鼠的肿瘤发展,并使外周血中CD3e-NK1.1+细胞比例提高113.0%,CD3e+CD28+细胞比例提高84.7%。CTP改善了Apc Min/+小鼠肠道微生物群的丰富度、多样性和均匀度,特别是通过调节免疫相关微生物的丰度。CTP有效调节了免疫相关细胞因子的表达,如白细胞介素(IL)-2(增加15.19%)、IL-12(增加17.47%)和转化生长因子(TGF)-β(降低11.19%)。
此外,它还提高了Apc Min/+小鼠脾脏和肿瘤中CD4和CD8的水平,以及辅助性T淋巴细胞(Th)1/Th2的比例。在CTP处理的小鼠中,观察到程序性死亡-1(PD-1)、程序性细胞死亡配体1(PD-L1)、细胞毒性T淋巴细胞相关抗原4(CTLA4)、活化T细胞核因子1(NFAT1)和核因子κB(NF-κB)p65信号水平降低。
总之,CTP的抗CRC作用与调节肠道微生物群介导的免疫功能有关,这为CTP作为治疗药物或联合药物用于临床CRC治疗提供了参考。
Calf thymus polypeptide (CTP), with a molecular mass of <10 kDa, is prepared from the thymus of less than 30-day-old newborn cattle. In the present study, the inhibitory function of CTP in colorectal cancer (CRC) was investigated in B6/JGpt- Apc em1Cin(MinC) /Gpt ( Apc Min/+ ) mice. CTP hampered tumor development and enhanced the ratio of CD3e - NK1. 1 + cells by 113. 0% and CD3e + CD28 + cells by 84.
7% in the peripheral blood of Apc Min/+ mice. CTP improved the richness, diversity, and evenness of the intestinal microbiota of Apc Min/+ mice, particularly by regulating the abundance of immune-related microorganisms. CTP effectively regulated the expression of immune-related cytokines, such as interleukin (IL)-2 (15. 19% increment), IL-12 (17. 47% increment), and transforming growth factor (TGF)-β (11. 19% reduction).
Additionally, it enhanced the levels of CD4 and CD8, as well as the ratio of helper T lymphocytes (Th)1/Th2 in the spleen and tumors of Apc Min/+ mice. In CTP-treated mice, reduced levels of programmed death-1 (PD-1), programmed cell death-ligand 1 (PD-L1), cytotoxic T lymphocyte-associated antigen 4 (CTLA4), activated nuclear factor of activated T cells 1 (NFAT1), and nuclear factor κB (NF-κB) p65 signaling were noted.
Collectively, the anti-CRC effect of CTP is related to the modulation of intestinal microbiota-mediated immune function, which provides a reference for CTP as a therapeutic drug or a combination drug used in CRC treatment in a clinical setting.
在 PubMed 查看 → 出版商原文(DOI) 全文 PDF(PMC)· 可下载 治疗专题与资料阅读指南 资料来源与翻译说明 报告译文或资料问题 →
MEMBER ACCOUNT
登录成功会直接打开下一页。