Journal Article

PD-L1 Dysregulation in COVID-19 Patients

Cicala, Claudia, Conti, Valeria, De Bellis, Emanuela, Filippelli, Amelia, Salzano, Francesco Antonio, Ciccarelli, Michele, Franci, Gianluigi, Caputo, Alessandro, Vecchione, Carmine, Pepe, Stefano, Masullo, Alfonso, Zannella, Carla, Pagliano, Pasquale, Peluso, Ilaria, Sabbatino, Francesco, Sellitto, Carmine, Greco, Giuseppe, Manzo, Valentina, Zeppa, Pio, Scognamiglio, Giosuè

2021

Overview

The COVID-19 pandemic has reached direct and indirect medical and social consequences with a subset of patients who rapidly worsen and die from severe-critical manifestations. As a result, there is still an urgent need to identify prognostic biomarkers and effective therapeutic approaches. Severe-critical manifestations of COVID-19 are caused by a dysregulated immune response. Immune checkpoint molecules such as Programmed death-1 (PD-1) and its ligand programmed death-ligand 1 (PD-L1) play an important role in regulating the host immune response and several lines of evidence underly the role of PD-1 modulation in COVID-19. Here, by analyzing blood sample collection from both hospitalized COVID-19 patients and healthy donors, as well as levels of PD-L1 RNA expression in a variety of model systems of SARS-CoV-2, including in vitro tissue cultures, ex-vivo infections of primary epithelial cells and biological samples obtained from tissue biopsies and blood sample collection of COVID-19 and healthy individuals, we demonstrate that serum levels of PD-L1 have a prognostic role in COVID-19 patients and that PD-L1 dysregulation is associated to COVID-19 pathogenesis. Specifically, PD-L1 upregulation is induced by SARS-CoV-2 in infected epithelial cells and is dysregulated in several types of immune cells of COVID-19 patients including monocytes, neutrophils, gamma delta T cells and CD4+ T cells. These results have clinical significance since highlighted the potential role of PD-1/PD-L1 axis in COVID-19, suggest a prognostic role of PD-L1 and provide a further rationale to implement novel clinical studies in COVID-19 patients with PD-1/PD-L1 inhibitors.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: adaptive immune response / Apoptosis / Biopsy / Cancer / CD4 antigen / COVID-19 / Epithelial cells / Genomes / Immune checkpoint / immune checkpoint molecules / Immune response / Immunology / Immunomodulation / Infections / Informed consent / innate immune response / Kinases / Leukocytes (neutrophilic) / Ligands / Lymphocytes T / Monocytes / Pandemics / Patients / PD-1 protein / PD-L1 / PD-L1 protein / Pneumonia / Respiratory distress syndrome / SARS-CoV-2 / Serum levels / Severe acute respiratory syndrome coronavirus 2 / Statistical analysis