肠菌移植联合免疫检查点抑制剂在终末期恶性肿瘤患者治疗中的探索性研究  

Exploratory study of fecal microbiota transplantation combined with immune checkpoint inhibitors in the treatment of end-stage malignant tumor patients

作　　者：储云茜 薛雅 蒋华[1] 戚春建[1] 戴菡珏 仙晴颖 朱文宇 CHU Yunqian;XUE Ya;JIANG Hua;QI Chunjian;DAI Hanjue;XIAN Qingying;ZHU Wenyu(The Affiliated Changzhou N0.2 People's Hospital of Nanjing Medical University,Changzhou 213100,Jiangsu,China)

机构地区：[1]南京医科大学附属常州市第二人民医院肿瘤中心,江苏常州213100

出　　处：《中国临床药理学与治疗学》2025年第4期509-516,共8页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：江苏省卫生健康委科研项目(ZD2022035);南京医科大学项目(NMUB20210052)。

摘　　要：目的:探讨对于多线抗肿瘤治疗失败合并恶液质的恶性肿瘤患者,予以肠菌移植联合免疫检查点抑制剂(ICIs)的疗效及安全性,探索患者血清免疫及肠道微生物环境的变化。方法:入组5例多线抗肿瘤治疗后失败的恶液质肿瘤患者,予以特瑞普利单抗联合肠菌移植治疗,每2~3周期进行疗效评估,观察患者不良反应并动态检测粪便16srRNA基因测序、血清免疫学指标。结果:除1名患者因入组时肿瘤负荷过大在移植2.5个月后死亡,其余4名患者的总生存期延长(7.4、8.3、28.5、52.3个月),1名肺腺癌颅内多发转移患者在肠菌移植后颅内转移病灶明显缩小,几乎消失。患者血清IL-2、IL-10、TGF-β等指标随着移植时间的增长,先迅速升高后缓慢降低,最终高于移植前,有统计学差异。16srRNA基因测序发现移植后患者总体肠道菌群结构分布出现明显差异,并逐渐向健康移植的供体靠拢,普拉梭菌可能是该类患者免疫治疗的疗效预测标志物。所有患者未出现2级以上不良反应,安全性良好。结论:肠菌移植联合免疫治疗或可改善生活质量、血清免疫环境及肠道微生物构成,对生存预后带来积极影响,且安全可控,为终末期恶液质患者开拓新的治疗手段。AIM:To explore the efficacy and safety of fecal microbiota transplantation combined with immune checkpoint inhibitors(ICIs)for malignant tumor patients with failed multi line antitumor treatment and concomitant cachexia,and to explore the changes in blood immunity and intestinal microbial environment in patients.METHODS:Five patients with malignant tumors who failed multi line anti-tumor treatment were enrolled and treated with ICIs combined with fecal microbiota transplantation.The efficacy was evaluated every 2-3 cycles,and adverse reactions were observed.Fecal 16srRNA gene sequencing and serum immunological indicators were dynamically detected.RESULTS:Except for one patient who died 2.5 months after transplantation due to excessive tumor burden at enrollment,the overall survival of the remaining four patients were extended(7.4,8.3,28.5,52.3 months).One patient with multiple intracranial metastases of lung adenocarcinoma significantly reduced the intracranial metastasis after intestinal microbiota transplantation and almost disappeared.The serum IL-2,IL-10,TGFβand other indicators of patients increased rapidly and then slowly decreased with the increase of transplantation time,and finally were higher than before transplantation,with statistical differences.16srRNA gene sequencing analysis revealed significant differences in the overall distribution of gut microbiota in patients after transplantation,gradually approaching healthy transplant donors.All patients did not experience grade 2 or above adverse reactions,and the safety was good.CONCLUSION:For patients with malignant tumors,the combination of fecal microbiota transplantation and immunotherapy may improve their quality of life,serum immune environment,and intestinal microbiota composition,have a positive impact on survival prognosis,and are safe and controllable,opening up new treatment methods for end-stage patients.

关 键 词：肠菌移植 免疫检查点抑制剂 多线治疗 恶性肿瘤 

分 类 号：R73[医药卫生—肿瘤]