Saha Aditi, Dreyfuss Isabella, Sarfraz Humaira, Friedman Mark, Markowitz Joseph
Department of Cutaneous Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
Cancers (Basel). 2022 Dec 23;15(1):84. doi: 10.3390/cancers15010084.
Checkpoint molecules are cell surface receptors on immune cells that mitigate excessive immune responses, but they have increased expression levels in cancer to facilitate immune escape. Checkpoint blockade therapies (e.g., anti-PD-1, anti-CTLA-4, and anti-LAG-3 therapy, among others) have been developed for multiple cancers. Colitis associated with checkpoint blockade therapy has pathophysiological similarities to inflammatory bowel disease (IBD), such as Crohn's disease and ulcerative colitis. Current therapeutic guidelines for checkpoint blockade-induced colitis include corticosteroids and, if the patient is refractory to steroids, immunomodulating antibodies, such as anti-TNF and anti-integrin agents. Interestingly, immunomodulatory molecules, such as TNFα, are upregulated in both IBD and checkpoint-mediated colitis. The inflammatory colitis toxicity symptoms from checkpoint blockade are similar to clinical symptoms experienced by patients with IBD. The pathophysiologic, dietary, and genetic factors associated with IBD will be reviewed. We will then explain how the principles developed for the treatment of IBD can be applied to patients experiencing inflammatory bowel toxicity secondary to checkpoint blockade.
检查点分子是免疫细胞表面的受体,可减轻过度的免疫反应,但它们在癌症中的表达水平会升高,以促进免疫逃逸。已经针对多种癌症开发了检查点阻断疗法(例如抗PD-1、抗CTLA-4和抗LAG-3疗法等)。与检查点阻断疗法相关的结肠炎在病理生理学上与炎症性肠病(IBD)相似,如克罗恩病和溃疡性结肠炎。目前针对检查点阻断引起的结肠炎的治疗指南包括使用皮质类固醇,如果患者对类固醇难治,则使用免疫调节抗体,如抗TNF和抗整合素药物。有趣的是,免疫调节分子,如TNFα,在IBD和检查点介导的结肠炎中均上调。检查点阻断引起的炎症性结肠炎毒性症状与IBD患者经历的临床症状相似。将回顾与IBD相关的病理生理、饮食和遗传因素。然后我们将解释如何将为治疗IBD而制定的原则应用于因检查点阻断继发炎症性肠毒性的患者。