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免疫检查点抑制剂治疗肺腺癌后 67 岁男性患奇异分枝杆菌肺病:免疫失调引起的感染?

Non-tuberculous mycobacteria lung disease due to Mycobacterium chimaera in a 67-year-old man treated with immune checkpoint inhibitors for lung adenocarcinoma: infection due to dysregulated immunity?

机构信息

Infectious Diseases Unit, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

Department of Pathophysiology and Transplantation, University of Milan, Via Francesco Sforza 35, Milan, Italy.

出版信息

BMC Infect Dis. 2023 Sep 4;23(1):573. doi: 10.1186/s12879-023-08537-w.

Abstract

Immune checkpoint inhibitors (ICIs) are drugs growingly employed in cancer immunotherapy which have significantly improved the prognosis of several tumours. ICIs act by restoring the "exhausted" immune system and increasing the number of T cells active against pathogens losing tolerogenic signalling, which has been linked to an increased risk of infectious events. We present the case of a 67-year-old man with locally advanced lung adenocarcinoma treated with the anti-PD-L1 durvalumab. Three months after immunotherapy started, an apparent radiological progression was found with elements suggesting a parenchymal superinfection associated with weight loss, asthenia, and sputum emission. A bronchoalveolar lavage resulted positive for Mycobacterium chimaera, and treatment with amikacin iv (for eight weeks) and daily azithromycin, ethambutol, and rifampicin was started. Thirteen months after treatment started, the patient is alive with a stable lung condition. The case highlights the risk of non-tuberculous mycobacteria lung disease (NTM-LD) in patients receiving ICIs treatment. We hypothesise that durvalumab induced an exaggerated immune response toward the mycobacteria, leading to immunopathology and overt clinical manifestations. Clinicians should be aware of this possibility in patients receiving ICIs developing new signs/symptoms related to the respiratory tract, especially in countries with a high prevalence of NTM-LD.

摘要

免疫检查点抑制剂(ICIs)是癌症免疫治疗中越来越多地使用的药物,它们显著改善了几种肿瘤的预后。ICIs 通过恢复“耗竭”的免疫系统并增加针对失去耐受信号的病原体的 T 细胞数量来发挥作用,这与感染事件风险增加有关。我们报告了一例局部晚期肺腺癌患者,该患者接受了抗 PD-L1 的 durvalumab 治疗。免疫治疗开始三个月后,发现明显的影像学进展,有迹象表明与体重减轻、乏力和咳痰有关的实质部继发感染。支气管肺泡灌洗液检测出 Chimaera 分枝杆菌阳性,开始静脉注射阿米卡星(八周)和每日阿奇霉素、乙胺丁醇和利福平治疗。治疗开始后 13 个月,患者仍存活且肺部状况稳定。该病例强调了接受 ICI 治疗的患者发生非结核分枝杆菌肺病(NTM-LD)的风险。我们假设 durvalumab 诱导针对分枝杆菌的过度免疫反应,导致免疫病理学和明显的临床表现。临床医生应注意这种可能性,即接受 ICI 治疗的患者出现与呼吸道相关的新症状/体征,特别是在 NTM-LD 高发的国家。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a8c/10476418/f3acc4b2e46d/12879_2023_8537_Fig1_HTML.jpg

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