Department of Gastroenterology, Kremlin Bicêtre Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Le Kremlin Bicêtre, France.
Université Paris-Sud, Faculté de Médecine, Le Kremlin Bicêtre, F-94276, France.
Semin Immunopathol. 2017 Apr;39(3):327-331. doi: 10.1007/s00281-016-0613-x. Epub 2017 Jan 16.
Checkpoint inhibitors blocking CTLA-4 (ipilimumab) and PD-1 (nivolumab, pembrolizumab) have transfigured our cancer treatment paradigm. However, these drugs can induce immune-related adverse events that share clinical and pathological characteristics with immune-mediated diseases. One of the most severe immune-related adverse event observed with anti-CTLA-4 is an enterocolitis that mirrors naturally occurring inflammatory bowel disease. This paper reviews the clinical, immunological, and microbiota data associated with the immune-related enterocolitis induced by the cancer immunotherapy blocking CTLA-4, ipilimumab. A parallel analysis of the mechanisms underlying inflammatory bowel diseases on the one hand, and anti-CTLA-4-induced colitis on the other hand, stresses the crucial role of the gut microbiota and of resident T in the genesis of both iatrogenic and spontaneous inflammatory bowel diseases.
检查点抑制剂阻断 CTLA-4（伊匹单抗）和 PD-1（纳武单抗、派姆单抗）改变了我们的癌症治疗模式。然而，这些药物会引发免疫相关的不良反应，其临床表现和病理学特征与免疫介导的疾病相似。抗 CTLA-4 最严重的免疫相关不良反应之一是类似于特发性炎症性肠病的结肠炎。本文综述了与癌症免疫治疗阻断 CTLA-4（伊匹单抗）引起的免疫相关结肠炎相关的临床、免疫学和微生物组数据。对一方面炎症性肠病的发病机制，以及另一方面抗 CTLA-4 诱导结肠炎的发病机制进行平行分析，强调了肠道微生物组和固有 T 细胞在这两种医源性和自发性炎症性肠病发病机制中的关键作用。
