Immune-checkpoint inhibitors (ICIs) have improved clinical outcomes and are becoming a standard treatment for many cancer types. However, these drugs also induce immune-related adverse events, among which interstitial lung disease (ILD) is potentially fatal. The underlying mechanism of ILD induction by ICIs is largely unknown. With the use of flow cytometry, we determined the expression levels of the immune-checkpoint proteins PD-1, TIM-3, TIGIT, LAG-3 and PD-L1 in T cells of bronchoalveolar lavage fluid (BALF) from patients with ICI-related ILD and compared them with those for patients with sarcoidosis or with ILD related to connective tissue disease or cytotoxic drug use. The proportions of CD8⁺ T cells positive for both PD-1 and TIM-3 or for TIGIT in BALF were significantly higher for ICI-related ILD patients than for those with other types of ILD. A prominent increase in the proportion of PD-1⁺PD-L1⁺ cells among CD8⁺ T cells was also apparent in BALF of a patient with a fatal case of ICI-related ILD, and the proportion of such cells was positively correlated with the grade of ICI-related ILD. Our data reveal the immune-checkpoint profiles of T cells in ICI-related ILD and may provide mechanistic insight into the development of this adverse event.

中文翻译：

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免疫检查点抑制剂相关间质性肺病患者支气管肺泡灌洗液中 T 细胞的免疫检查点谱。

免疫检查点抑制剂 (ICI) 改善了临床结果，并正在成为许多癌症类型的标准治疗方法。然而，这些药物也会诱发免疫相关的不良事件，其中间质性肺病 (ILD) 可能是致命的。ICIs诱导ILD的潜在机制在很大程度上是未知的。使用流式细胞术，我们确定了 ICI 患者支气管肺泡灌洗液 (BALF) T 细胞中免疫检查点蛋白 PD-1、TIM-3、TIGIT、LAG-3 和 PD-L1 的表达水平。相关的 ILD 并将其与结节病患者或与结缔组织病或细胞毒性药物使用相关的 ILD 患者进行比较。CD8 ⁺的比例ICI 相关 ILD 患者的 PD-1 和 TIM-3 或 BALF 中的 TIGIT 阳性 T 细胞显着高于其他类型 ILD 患者。一例 ICI 相关 ILD 致死病例的 BALF中 CD8 ⁺ T 细胞中 PD-1 ⁺ PD-L1 ⁺细胞的比例显着增加，并且该细胞的比例与ICI 相关 ILD 的分级。我们的数据揭示了 ICI 相关 ILD 中 T 细胞的免疫检查点谱，并可能提供对该不良事件发展的机制洞察。