Fecal Microbiota Transplantation for Immune Checkpoint Inhibitor-Induced Colitis Is Safe and Contributes to Recovery: Two Case Reports.

IF 3.2 4区 医学 Q3 IMMUNOLOGY
Bas Groenewegen, Elisabeth M Terveer, Arjen Joosse, Marieke C Barnhoorn, Romy D Zwittink
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Abstract

Immune checkpoint inhibitors (ICIs) have improved the prognosis in multiple cancer types. However, ICIs can induce immune-related adverse events such as immune-mediated enterocolitis (IMC). The gut microbiota may be implicated in IMC development. Therefore, we investigated fecal microbiota transplantation (FMT) as a treatment option for 2 patients with metastatic cancer suffering from refractory IMC. The patients were treated with, respectively, 1 and 3 FMTs after vancomycin pre-treatment. We monitored defecation frequency, fecal calprotectin, and microbiota composition. After FMT, both patients improved in defecation frequency, were discharged from the hospital, and received lower dosage of immunosuppressive therapy. Patient 1 developed an invasive pulmonary aspergillosis deemed to be related to prolonged steroid exposure. Patient 2 suffered from a Campylobacter jejuni infection after the first FMT and was treated with meropenem, resulting in a low-diversity microbiota profile and increased calprotectin levels and defecation frequency. After a second and third FMT, bacterial diversity increased and defecation frequency and calprotectin levels decreased. Pre-FMT, both patients showed low bacterial richness, but varying bacterial diversity. After FMT, diversity and richness were similar to healthy donor levels. In conclusion, FMT resulted in improvement of IMC symptoms and corresponding microbial changes in 2 cancer patients with refractory IMC. While more research is warranted, microbiome-modulation could be a promising new therapeutic option for IMC.

粪便微生物群移植治疗免疫检查点抑制剂诱导的结肠炎是安全的,并有助于恢复:两例报告
免疫检查点抑制剂(ICIs)改善了多种癌症类型的预后。然而,ICIs可诱导免疫相关不良事件,如免疫介导性小肠结肠炎(IMC)。肠道微生物群可能与IMC的发展有关。因此,我们研究了粪便微生物群移植(FMT)作为2例转移性癌症合并难治性IMC的治疗选择。在万古霉素预处理后,患者分别接受1次和3次fmt治疗。我们监测排便频率、粪钙保护蛋白和微生物群组成。经FMT治疗后,两例患者排便次数均有所改善,出院,并接受较低剂量的免疫抑制治疗。患者1发生侵袭性肺曲霉病,认为与长期使用类固醇有关。患者2在第一次FMT后出现空肠弯曲杆菌感染,并使用美罗培南治疗,导致微生物群多样性低,钙保护蛋白水平升高和排便频率增加。在第二次和第三次FMT后,细菌多样性增加,排便频率和钙保护蛋白水平下降。fmt前,两例患者均显示细菌丰富度低,但细菌多样性不同。FMT后,多样性和丰富度与健康供体水平相似。综上所述,FMT改善了2例难治性IMC患者的IMC症状和相应的微生物变化。虽然需要进行更多的研究,但微生物组调节可能是一种有希望的治疗IMC的新选择。
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来源期刊
Journal of Immunotherapy
Journal of Immunotherapy 医学-免疫学
CiteScore
6.90
自引率
0.00%
发文量
79
审稿时长
6-12 weeks
期刊介绍: Journal of Immunotherapy features rapid publication of articles on immunomodulators, lymphokines, antibodies, cells, and cell products in cancer biology and therapy. Laboratory and preclinical studies, as well as investigative clinical reports, are presented. The journal emphasizes basic mechanisms and methods for the rapid transfer of technology from the laboratory to the clinic. JIT contains full-length articles, review articles, and short communications.
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