Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, China.
Medical Doctor Program, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, China.
Thorac Cancer. 2022 Oct;13(19):2681-2691. doi: 10.1111/1759-7714.14626. Epub 2022 Aug 31.
Immunotherapy has dramatically revolutionized the therapeutic landscape for patients with cancer. Although immune checkpoint inhibitors are now accepted as effective anticancer therapies, they introduce a novel class of toxicity, termed immune-related adverse events, which can lead to the temporary or permanent discontinuation of immunotherapy and life-threatening tumor progression. Therefore, the effective prevention and treatment of immune-related adverse events is a clinical imperative to maximize the utility of immunotherapies. Immune-related adverse events are related to the intestinal microbiota, baseline gut microbiota composition is an important determinant of immune checkpoint inhibitor-related colitis, and antibiotics exacerbate these undesirable side-effects. Supplementation with specific probiotics reduces immune checkpoint inhibitor-related colitis in mice, and fecal microbiota transplantation has now been shown to effectively treat refractory immune checkpoint inhibitor-related colitis in the clinic. Hence, modifying the microbiota holds great promise for preventing and treating immune-related adverse events. Microbiomes and their metabolites play important roles in the potential underlying mechanisms through interactions with both innate and adaptive immune cells. Here we review the gut microbiota and immune regulation; the changes occurring in the microbiota during immune checkpoint inhibitor therapy; the relationship between the microbiota and immune-related adverse events, antibiotics, probiotics/prebiotics, and fecal microbiota transplantation in immune checkpoint inhibitor-related colitis; and the protective mechanisms mediated by the microbiome and metabolites in immune-related adverse events.
免疫疗法极大地改变了癌症患者的治疗前景。虽然免疫检查点抑制剂现在被认为是有效的抗癌疗法，但它们会引起一类新的毒性，称为免疫相关不良反应，这可能导致免疫治疗的暂时或永久停止，并危及生命的肿瘤进展。因此，有效预防和治疗免疫相关不良反应是最大限度发挥免疫疗法效用的临床当务之急。免疫相关不良反应与肠道微生物群有关，基线肠道微生物群组成是免疫检查点抑制剂相关结肠炎的重要决定因素，抗生素会加重这些不良副作用。补充特定的益生菌可减少小鼠的免疫检查点抑制剂相关结肠炎，粪便微生物群移植现已在临床上显示可有效治疗难治性免疫检查点抑制剂相关结肠炎。因此，改变微生物群在预防和治疗免疫相关不良反应方面具有很大的前景。微生物组及其代谢物通过与先天和适应性免疫细胞相互作用，在潜在的潜在机制中发挥重要作用。在这里，我们回顾了肠道微生物群和免疫调节；在免疫检查点抑制剂治疗过程中微生物群发生的变化；微生物群与免疫相关不良反应、抗生素、益生菌/益生元、免疫检查点抑制剂相关结肠炎中的粪便微生物群移植的关系；以及微生物组和代谢物在免疫相关不良反应中的保护机制。
