Age-dependent hypoxia-induced PD-L1 upregulation in patients with obstructive sleep apnoea.

Abstract

BACKGROUND AND OBJECTIVE:

In obstructive sleep apnoea (OSA), intermittent hypoxia (IH) compromises immune surveillance through the upregulation of the programmed cell death-1 (PD-1) receptor and its ligand (PD-L1). Because the risk of OSA-related cancer depends on age, we assessed PD-L1/PD-1 expression in middle-aged and older patients with OSA as well as in a murine model.

METHODS:

PD-L1 expression was studied in 41 patients with severe OSA and 40 healthy volunteers (HV), divided into two groups (≤55 and >55 years of age). We used flow cytometry, quantitative PCR (qPCR) and ELISA to determine PD-L1 expression on monocytes and plasma PD-L1 protein levels. Moreover, we analysed PD-L1 expression on an in vivo IH model with old and young mice.

RESULTS:

In subjects up to 55 years of age, severe OSA increased PD-L1 surface protein and mRNA level expression on monocytes and soluble-PD-L1 protein concentration in plasma compared to HV. PD-L1 and hypoxia-induced factor (HIF)-1α expression correlated with age in HV, whereas in patients with OSA there was a negative relationship. In the mice exposed to IH, PD-L1 expression on F4/80+ splenocytes was also only increased in young animals. HIF-1α expression was significantly higher in patients with OSA than in HV in subjects up to 55 years of age, while PD-L1 expression in monocytes was related to HIF-1α expression in young patients with OSA.

CONCLUSION:

PD-L1 upregulation in patients with OSA as a consequence of HIF-1α activation occurs mainly in young patients. In older patients with OSA, upregulation was not detected, possibly due to impaired oxygen sensitivity.

• Authors: Carolina Cubillos-Zapata, Cristina Balbás-García, Jose Avendaño-Ortiz, Victor Toledano, Marta Torres, Isaac Almendros, Raquel Casitas, Ester Zamarrón, Aldara García-Sánchez, Jaime Feliu, Luis A Aguirre, Ramón Farre, Eduardo López-Collazo, Francisco García-Rio
• Journal: Respirology (Carlton, Vic.) (Respirology) Vol. 24 Issue 7 Pg. 684-692 (07 2019) ISSN: 1440-1843 [Electronic] Australia
• PMID: 30656807 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 Asian Pacific Society of Respirology.

Chemical References

• B7-H1 Antigen
• CD274 protein, human
• Cd274 protein, mouse
• HIF1A protein, human
• Hypoxia-Inducible Factor 1, alpha Subunit
• RNA, Messenger

Topics

• Adult
• Age Factors
• Aged
• Animals
• B7-H1 Antigen (blood, genetics)
• Case-Control Studies
• Female
• Humans
• Hypoxia (blood, etiology, physiopathology)
• Hypoxia-Inducible Factor 1, alpha Subunit (blood, genetics)
• Male
• Mice
• Middle Aged
• Monocytes (metabolism)
• RNA, Messenger
• Sleep Apnea, Obstructive (blood, complications, physiopathology)
• Transcriptional Activation
• Up-Regulation