Thoracic Surgery and Lung Transplantation Unit, Department of Cardio- Thoracic - Vascular Disease, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Division of Pathology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Front Immunol. 2023 Jan 10;13:1024021. doi: 10.3389/fimmu.2022.1024021. eCollection 2022.
Chronic lung allograft dysfunction (CLAD) is the main cause of the reduced survival of lung transplanted (LTx) patients. The possible role of immune checkpoint molecules in establishing tolerance has been scarcely investigated in the setting of lung transplantation.
We conducted a retrospective, observational pilot study on a consecutive series of transbronchial cryobiopsies (TCB) obtained from 24 patients during LTx follow-up focusing on PD-1, one of the most investigated immune checkpoint molecules.
Results showed that PD-1-expressing T lymphocytes were present in all TCB with a histological diagnosis of acute rejection (AR; 9/9), but not in most (11/15) of the TCB not resulting in a diagnosis of AR (p=0.0006). Notably, the presence of PD-1-expressing T lymphocytes in TCB resulted in a 10-times higher risk of developing chronic lung allograft dysfunction (CLAD), the main cause of the reduced survival of lung transplanted patients, thus being associated with a clearly worst clinical outcome.
Results of this pilot study indicate a central role of PD-1 in the development of AR and its evolution towards CLAD and suggest that the evaluation of PD-1-expressing lymphocytes in TCB could offer a prognostic advantage in monitoring the onset of AR in patients who underwent lung transplantation.
慢性肺移植物功能障碍（CLAD）是导致肺移植（LTx）患者生存率降低的主要原因。免疫检查点分子在建立耐受中的可能作用在肺移植中鲜有研究。
我们对 24 例 LTx 随访期间经支气管冷冻活检（TCB）进行了回顾性、观察性的初步研究，重点关注 PD-1，这是研究最多的免疫检查点分子之一。
结果表明，所有具有急性排斥反应（AR）组织学诊断的 TCB（9/9）中均存在表达 PD-1 的 T 淋巴细胞，但大多数未诊断为 AR 的 TCB 中（11/15）不存在（p=0.0006）。值得注意的是，TCB 中表达 PD-1 的 T 淋巴细胞的存在使发生慢性肺移植物功能障碍（CLAD）的风险增加了 10 倍，CLAD 是肺移植患者生存率降低的主要原因，因此与更差的临床结局相关。
这项初步研究的结果表明 PD-1 在 AR 的发生及其向 CLAD 的发展中起核心作用，并表明在 TCB 中评估表达 PD-1 的淋巴细胞可在监测肺移植患者 AR 发生时提供预后优势。
