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肠道微生态特征与晚期MSS型消化道肿瘤免疫治疗疗效的相关性

Correlation Between Gut Microbiota Characteristics and Immunotherapy Efficacy in Patients with Advanced Microsatellite Stable Gastrointestinal Tumors

  • 摘要:
    目的 探讨晚期微卫星稳定(MSS)型消化道肿瘤患者肠道微生态与免疫治疗疗效的相关性。
    方法 纳入2022年11月1日至2025年7月31日收治的晚期MSS型消化道肿瘤患者30例,其中胃癌14例、结直肠癌16例。所有患者均接受肠道微生态检测,并根据检测结果给予相应干预,后续采用抗肿瘤血管生成药物联合免疫治疗,部分患者联合益生菌或粪菌移植(FMT)。主要观察终点为客观缓解率(ORR)及疾病控制率(DCR),次要终点为无进展生存期(PFS)和总生存期(OS)。采用单因素及多因素Cox回归分析评估潜在预后因素。
    结果 30例患者中无完全缓解(CR)病例,部分缓解(PR)2例,疾病稳定(SD)12例,疾病进展(PD)16例。ORR为6.7%,DCR为46.7%,中位PFS为6.4个月,中位OS为8.3个月。2例PR患者肠道微生态检测结果均为菌群紊乱中风险,肠型均为拟杆菌肠型。多因素分析显示,肿瘤类型、肝转移及骨转移是PFS和OS的潜在预后因素。
    结论 肠道微生态紊乱程度为中风险的患者对免疫治疗的反应相对较好,提示肠道菌群状态或可作为预测晚期MSS型消化道肿瘤免疫治疗疗效的潜在生物标志物。

     

    Abstract:
    Objective To investigate the correlation between gut microbiota characteristics and immunotherapy efficacy in patients with advanced microsatellite stable (MSS) advanced gastrointestinal tumors.
    Methods Thirty patients with advanced MSS gastrointestinal tumors, including fourteen cases of gastric cancer and sixteen cases of colorectal cancer, who were admitted from November 1, 2022, to July 31, 2025 were enrolled. All patients underwent gut microbiota testing and received corresponding interventions on the basis of the results, followed by treatment with antiangiogenic agents combined with immunotherapy. Some patients additionally received probiotics or fecal microbiota transplantation. The primary endpoints were disease control rate (DCR) and objective response rate (ORR). The secondary endpoints were progression-free survival (PFS) and overall survival (OS). Univariate and multivariate Cox regression analyses were used to assess potential prognostic factors.
    Results Among the thirty patients, no complete response was observed. Two cases of partial response (PR), twelve cases of stable disease, and sixteen cases of progressive disease were recorded. The ORR was 6.7%, and the DCR was 46.7%. The median PFS was 6.4 months, and the median OS was 8.3 months. Both PR patients were classified as having a medium risk of gut microbiota dysbiosis and exhibited a Bacteroides-dominated enterotype. Multivariate analysis indicated that tumor type, liver metastasis, and bone metastasis were potential prognostic factors for PFS and OS. Conclusion Patients with a medium risk of gut dysbiosis may exhibit a relatively favorable response to immunotherapy, suggesting that gut microbiota status could serve as a potential biomarker for predicting treatment efficacy in advanced MSS gastrointestinal tumors.

     

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