PD-L1 and PD-1 Are Associated with Clinical Outcomes and Alveolar Immune Cell Activation in Acute Respiratory Distress Syndrome

Morrell, Eric D.; Holton, Sarah E.; Wiedeman, Alice; Kosamo, Susanna; Mitchem, Mallorie A.; Dmyterko, Victoria; Franklin, Zoie; Garay, Ashley; Stanaway, Ian B.; Liu, Ted; Sathe, Neha A.; Mabrey, F. Linzee; Stapleton, Renee D.; Malhotra, Uma; Speake, Cate; Hamerman, Jessica A.; Pipavath, Sudhakar; Evans, Laura; Bhatraju, Pavan K.; Long, S. Alice; Wurfel, Mark M.; Mikacenic, Carmen

doi:10.1165/rcmb.2024-0201oc

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2024

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Cited by 3 publications

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Monocyte programmed death-ligand 1 upregulation in early post-out-of-hospital cardiac arrest is associated with increased risk of acute respiratory distress syndrome

An,

Shao,

Hang

et al. 2024

Resuscitation Plus

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Monocyte programmed death-ligand 1 upregulation in early post-out-of-hospital cardiac arrest is associated with increased risk of acute respiratory distress syndrome

An,

Shao,

Hang

et al. 2024

Resuscitation Plus

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Balancing Act: PD-1, PD-L1, and the Inflammatory Tightrope of Acute Respiratory Distress Syndrome

Mould,

Janssen

2024

Am J Respir Cell Mol Biol

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Immune checkpoint dysregulation in COVID-19 pathogenesis and disease severity.

Villalba,

et al. 2024

Preprint

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Accumulating evidence suggests dysregulated immune checkpoint (IC) signaling can exacerbate COVID-19 severity, but the role of these molecules in the pathogenesis of fatal COVID-19-related diffuse alveolar damage (DAD) remains elusive. Understanding how IC proteins influence acute lung injury due to COVID-19 can provide insights into potential therapeutic strategies to modulate immune responses and improve patient outcomes. Here, in a single-center autopsy cohort, we determined the cellular localization of ICs in lung tissue from cases of fatal COVID-19, DAD-comparators, and non-fibrotic controls by using immunohistochemistry, and investigated their association with clinical outcomes. We expanded our findings by performing analyses of publicly available single-cell RNA sequencing datasets from patients with fatal COVID-19 and non-fibrotic controls. We demonstrated the presence of protein-protein interaction networks of ICs in the lung cellular niche by performing transcriptomic profiling of lung tissue-derived RNA counts from patients with fatal COVID-19. Further, we leveraged data from the largest international, multi-center COVID-19 autopsy cohort and validated that, among patients with fatal COVID-19, those with higher PD-L1/CD274 expression in lung endothelial cells had more rapid clinical deterioration. Lastly, in a cohort of individuals with early COVID-19, IC plasma protein levels were elevated in those with persistent SARS-CoV-2 RNAemia and adverse clinical outcomes. Collectively, our data provide unique pathological insights into the role of IC dysregulation and differential disease severity in COVID-19.

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PD-L1 and PD-1 Are Associated with Clinical Outcomes and Alveolar Immune Cell Activation in Acute Respiratory Distress Syndrome

Cited by 3 publications

References 46 publications

Monocyte programmed death-ligand 1 upregulation in early post-out-of-hospital cardiac arrest is associated with increased risk of acute respiratory distress syndrome

Monocyte programmed death-ligand 1 upregulation in early post-out-of-hospital cardiac arrest is associated with increased risk of acute respiratory distress syndrome

Balancing Act: PD-1, PD-L1, and the Inflammatory Tightrope of Acute Respiratory Distress Syndrome

Immune checkpoint dysregulation in COVID-19 pathogenesis and disease severity.

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