免疫检查点抑制剂（ICIs）在多种肿瘤治疗中的应用越来越多。不幸的是，免疫相关的不良事件影响多达60％的接受者，通常导致在少有其他癌症治疗选择的情况下中止治疗。检查点抑制剂所致结肠炎（ICI-colitis）是一种常见的毒性反应，其潜在机制尚不清楚。为了更好地了解结肠炎的进展和治疗过程中结肠特异性和外周免疫环境的变化，我们收集了一位患有梅尔克松细胞癌并在接受pembrolizumab治疗后出现结肠炎的患者的血液和结肠组织。我们对收集的样本进行了单细胞RNA测序和T细胞受体测序，并在pembrolizumab治疗前、期间和后以及各种干预措施后进行分析。我们报道了在结肠炎的不同阶段具有细胞毒性、记忆和增殖标志物的T细胞群体。我们显示生物治疗导致CD8+ T细胞的优先耗竭，并将循环和结肠驻留的T细胞亚群推测为炎症和对免疫抑制反应的潜在驱动因素。我们的发现强调了进一步探索结肠免疫环境的必要性，并将理性化未来评估免疫检查点抑制剂引起的结肠炎的生物治疗研究，包括在免疫检查点抑制剂再治疗的背景下。© 作者（或其雇主）2023。在CC BY-NC下允许再使用。不得进行商业再利用。由BMJ出版。

Immune checkpoint inhibitors (ICIs) are increasingly being used to manage multiple tumor types. Unfortunately, immune-related adverse events affect up to 60% of recipients, often leading to treatment discontinuation in settings where few alternative cancer therapies may be available. Checkpoint inhibitor induced colitis (ICI-colitis) is a common toxicity for which the underlying mechanisms are poorly defined. To better understand the changing colon-specific and peripheral immune environments over the course of progression and treatment of colitis, we collected blood and colon tissue from a patient with Merkel cell carcinoma who developed colitis on treatment with pembrolizumab. We performed single-cell RNA sequencing and T-cell receptor sequencing on samples collected before, during and after pembrolizumab and after various interventions to mitigate toxicity. We report T-cells populations defined by cytotoxicity, memory, and proliferation markers at various stages of colitis. We show preferential depletion of CD8+ T cells with biologic therapy and nominate both circulating and colon-resident T-cell subsets as potential drivers of inflammation and response to immune suppression. Our findings highlight the need for further exploration of the colon immune environment and rationalize future studies evaluating biologics for ICI-colitis, including in the context of ICI re-challenge.© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.