通过激活细胞毒性CD8 T细胞增强抗PD-1在结直肠癌中的疗效。
enhances anti-PD-1 efficacy in colorectal cancer by activating cytotoxic CD8 T cells.
作者信息
Chen Lu, Ruan Guangcong, Zhao Xuefei, Yi Ailin, Xiao Zhifeng, Tian Yuting, Cheng Yi, Chen Dongfeng, Wei Yanling
机构信息
Department of Gastroenterology, Chongqing Key Laboratory of Digestive Malignancies, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China.
出版信息
Front Immunol. 2025 Mar 21;16:1553757. doi: 10.3389/fimmu.2025.1553757. eCollection 2025.
BACKGROUND
Immune checkpoint therapy for colorectal cancer (CRC) has been found to be unsatisfactory for clinical treatment. Fecal microbiota transplantation (FMT) has been shown to remodel the intestinal flora, which may improve the therapeutic effect of αPD-1. Further exploration of key genera that can sensitize cells to αPD-1 for CRC treatment and preliminary exploration of immunological mechanisms may provide effective guidance for the clinical treatment of CRC.
METHODS
In this study, 16S rRNA gene sequencing was analyzed in the fecal flora of both responders and no-responders to αPD-1 treatment, and the therapeutic effect was experimentally verified.
RESULTS
was found to be highly abundant in the fecal flora of treated mice, and mannose-sensitive hemagglutinin (PA-MSHA) in combination with αPD-1 was effective in the treatment of CRC through the induction of CD8 T-cell immunological effects.
CONCLUSION
The clinical drug PA-MSHA can be used in combination with αPD-1 for the treatment of CRC as a potential clinical therapeutic option.
背景
已发现用于结直肠癌（CRC）的免疫检查点疗法在临床治疗中效果不尽人意。粪便微生物群移植（FMT）已被证明可重塑肠道菌群，这可能会提高αPD-1的治疗效果。进一步探索可使细胞对αPD-1敏感以用于CRC治疗的关键菌属，并初步探索免疫机制，可为CRC的临床治疗提供有效指导。
方法
在本研究中，对αPD-1治疗的应答者和无应答者的粪便菌群进行16S rRNA基因测序分析，并通过实验验证治疗效果。
结果
发现其在治疗小鼠的粪便菌群中含量很高，并且甘露糖敏感血凝素（PA-MSHA）与αPD-1联合使用可通过诱导CD8 T细胞免疫效应有效治疗CRC。
结论
临床药物PA-MSHA可与αPD-1联合用于治疗CRC，作为一种潜在的临床治疗选择。
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