检查点抑制剂肺炎（CIP）是一种潜在致命的不良事件，其特征是接受免疫检查点抑制剂治疗的癌症患者出现新的肺部浸润。本研究旨在探讨 CIP 中肺微生物群、失调代谢物和宿主免疫之间的相互作用。我们招募了 13 名住院 CIP 患者、11 名特发性肺纤维化 (IPF) 患者和 10 名新发非小细胞肺癌患者。收集支气管肺泡灌洗液样本进行16S rRNA基因测序。使用手动计数和流式细胞术确定免疫细胞的百分比。使用培养的小鼠脾细胞和人 T 细胞分析微生物群、代谢物和淋巴细胞之间的相互作用。变形菌门成为优势门，在 CIP 和 IPF 组中尤其丰富。弧菌、盐单胞菌、红树林弧菌和盐弧菌因其丰度模式具有区别性而成为主要微生物群。弧菌（r = 0.72，P-adj = 0.007）和盐单胞菌（r = 0.65，P-adj = 0.023）与淋巴细胞有很强的相关性。 CIP 组中的梅氏弧菌和植物红树林细菌比 IPF 组中更丰富。月桂酰肉碱是一种与主要微生物群共存的关键中间代谢产物，对小鼠和人类 T 细胞的细胞因子分泌具有强大的作用，特别是在体外增强 CD4 和 CD8 细胞的 IFN-γ 和 TNF-α 产生。与 CIP 中主要的肺部微生物群一起发生，可以在体外激活 T 细胞。这些发现提示肺微生物群和酰基肉碱代谢失调可能参与CIP的发病机制。该工作得到了北京大学人民医院科研发展基金（RDJ2022-15）和2020年省临床重点专科能力建设项目（呼吸科）的支持。医学）。版权所有 © 2024 作者。由 Elsevier B.V. 出版。保留所有权利。

Checkpoint inhibitor pneumonitis (CIP) is a potentially fatal adverse event characterized by new pulmonary infiltrates in cancer patients receiving immune checkpoint inhibitor therapy. This study aims to explore the interplay between lung microbiota, dysregulated metabolites, and host immunity in CIP.We recruited thirteen hospitalized CIP patients, eleven idiopathic pulmonary fibrosis (IPF) patients, and ten new-onset non-small cell lung cancer patients. Bronchoalveolar lavage fluid samples were collected for 16S rRNA gene sequencing. The percentages of immune cells were determined using manual counting and flow cytometry. Interactions among microbiota, metabolites, and lymphocytes were analyzed using cultured mouse splenocytes and human T cells.Proteobacteria emerged as the dominant phylum, notably abundant in both the CIP and IPF groups. Vibrio, Halomonas, Mangrovibacter, and Salinivibrio were the predominant microbiota because of their discriminative abundance patterns. Vibrio (r = 0.72, P-adj = 0.007) and Halomonas (r = 0.65, P-adj = 0.023) demonstrated strong correlations with lymphocytes. Vibrio metschnikovii and Mangrovibacter plantisponsors were more abundant in the CIP group than in the IPF group. Lauroylcarnitine, a key intermediary metabolite co-occurring with the predominant microbiota, exhibited a potent effect on cytokine secretion by mouse and human T cells, notably enhancing IFN-γ and TNF-α production from CD4 and CD8 cells in vitro.Lauroylcarnitine, co-occurring with the predominant lung microbiota in CIP, could activate T cells in vitro. These findings suggest potential involvement of lung microbiota and acylcarnitine metabolism dysregulation in the pathogenesis of CIP.This work was supported by Peking University People's Hospital Scientific Research Development Funds (RDJ2022-15) and Provincial Key Clinical Specialty Capacity Building Project 2020 (Department of the Respiratory Medicine).Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.