免疫检查点抑制剂诱发肺毒性的临床和组织病理学特征。

IF 3.4 3区 医学 Q1 PATHOLOGY
Ines Rolim, Antonio Lopez-Beltran, Joana Ip, Beatriz Nunes, Ricardo Coelho, Marcos Pantarotto, Nuno Gil, Carol Farver
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引用次数: 0

摘要

随着免疫检查点抑制剂(ICIs)的问世,癌症治疗进入了一个新时代,随之而来的是一系列新的免疫相关不良反应,这些不良反应影响了多达 40% 的患者。有关这些事件相关病理特征的文献仍然有限。因此,为了扩大我们对肺部病变组织病理学谱的了解,我们对 ICI 治疗期间或治疗后收集的 16 份非肿瘤性肺部样本进行了病例研究系列分析。在三个研究类别[ICI + 放疗与/或无化疗(RT-based)、ICI + 化疗(CT-based)、ICI-based 单药治疗(ICI-mono)]中评估了一组与四个不同 "区室"(肺间质、肺细胞、肺泡间隙和支气管粘膜)相关的预定义组织学特征、CD4/CD8 T 细胞比率以及免疫细胞中 SP263 PD-L1 的表达。我们的研究结果发现,在每个研究类别中,至少有一半的病例出现了肺间质增厚、肺间质淋巴细胞浸润、肺细胞脱屑、肺泡内纤维蛋白或泡沫巨噬细胞;在 4 例(基于 RT 的)、3 例(基于 CT 的)和 1 例(基于 ICI-mono 的)患者中出现了所有这五种特征。与基于 RT 的类别(44%)相比,基于 CT 的类别(80%)和 ICI-mono 的类别(100%)经常发现透明膜。此外,在三个研究类别中,几乎所有病例的 CD4/CD8 比值都小于 1。最后,在每个研究类别中,有50%或更多的病例出现SP263 PD-L1阳性表达。总之,我们的研究结果表明,接受 ICI 治疗的患者的组织病理学结果并不具有诊断意义,而且各不相同。此外,这些结果与最近的研究一致,显示接受 ICI 治疗的患者 CD8+ T 细胞亚群有所扩大,并突出了多种疗法的协同作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Clinical and histopathological features of immune checkpoint inhibitor-induced lung toxicity.

A new era in cancer therapy emerged with the arrival of immune-checkpoint inhibitors (ICIs), followed by a new cadre of immune-related adverse events that affect up to 40% of patients. Literature on the pathological features associated with these events is still limited. Therefore, to expand our knowledge of the histopathologic spectrum of pulmonary changes, we conducted a case study series analysis on 16 non-neoplastic lung samples collected during or after ICI therapy. A set of predefined histological features related to the four different "compartments" (interstitium, pneumocyte, alveolar space, and bronchial mucosa), the CD4/CD8 T cell ratio, and the SP263 PD-L1 expression in the immune cells was assessed in three study categories [ICI + radiotherapy with/without chemotherapy (RT-based), ICI + chemotherapy (CT-based), ICI-based monotherapy (ICI-mono)]. Our results identified interstitial thickening, interstitial lymphocytic infiltrate, pneumocyte desquamation, intra-alveolar fibrin, or foamy macrophages in at least half of the cases in each of the study categories; all five features were present in 4 (RT-based), 3 (CT-based) and 1 (ICI-mono) patients. Hyaline membrane was a frequent finding in CT-based (80%) and ICI-mono (100%) compared to RT-based (44%) category. Moreover, CD4/CD8 ratio was ≤ 1 for almost all cases of the three study categories. Finally, a positive SP263 PD-L1 expression was identified in 50% or more of each study category. In conclusion, our results indicate that histopathologic findings in patients treated with ICI therapy are not diagnostic and varied. Additionally, these results are in line with recent studies showing an expansion on CD8+ T cell subset in patients under ICI treatment and highlight the synergism of polytherapy.

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来源期刊
Virchows Archiv
Virchows Archiv 医学-病理学
CiteScore
7.40
自引率
2.90%
发文量
204
审稿时长
4-8 weeks
期刊介绍: Manuscripts of original studies reinforcing the evidence base of modern diagnostic pathology, using immunocytochemical, molecular and ultrastructural techniques, will be welcomed. In addition, papers on critical evaluation of diagnostic criteria but also broadsheets and guidelines with a solid evidence base will be considered. Consideration will also be given to reports of work in other fields relevant to the understanding of human pathology as well as manuscripts on the application of new methods and techniques in pathology. Submission of purely experimental articles is discouraged but manuscripts on experimental work applicable to diagnostic pathology are welcomed. Biomarker studies are welcomed but need to abide by strict rules (e.g. REMARK) of adequate sample size and relevant marker choice. Single marker studies on limited patient series without validated application will as a rule not be considered. Case reports will only be considered when they provide substantial new information with an impact on understanding disease or diagnostic practice.
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