Elevated programmed cell death-1 protein/ligand (PD-1/PD-L1) and variants are associated with susceptibility to multiple myeloma: a case-control study in the Chinese cohort

Abstract

Multiple myeloma (MM) is a malignant disorder characterised by progressive immune dysregulation. The importance of programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) in MM has been documented in various populations, but studies have been limited to the Chinese cohort. In the present study, we examined the role of PD-1/PDL-1 in large cohorts of Chinese patients with MM and healthy controls to reveal a possible association with MM. Three hundred thirty-four MM patients and 202 healthy age-sex-matched subjects were enrolled in the present study. Serum levels of PD-1 and PD-L1 were quantified by ELISA. Percentages of T cells (CD4⁺ and CD8⁺ T cells) expressing PD-1 receptor were assessed by flow cytometry. Variants in PD-L1 (rs4143815) and PD-1 gene (rs2227981, rs2227982, rs7421861 and rs11568821) were genotyped by PCR-RFLP method. Patients with multiple myeloma had higher levels of PD-1 and PDL-1 than healthy controls, indicating an important role for programmed cell death protein-1 and its ligand in the pathogenesis of MM. T cells expressing PD-1 receptors were also significantly higher in MM patients than in controls. Mutants for PD-L1 (rs4143815) and PD-1 (rs2227982 and rs7421861) polymorphisms were significantly more common in MM than in HC. Interestingly, PD-L1 (rs4143815) and PD-1 (rs2227982 and rs7421861) variants were linked to higher sPD-L1 and sPD-1 levels, respectively. PD-1/PD-L1 levels are significantly higher in MM patients and could be a promising biomarker for the disease. Variants of PD-L1 and PD-1 are linked to serum-soluble proteins and are associated with the development of MM.

Keywords:

• Multiple myeloma
• PD-1
• PDL-1
• flow cytometry
• Chinese
• gene polymorphism

Acknowledgments

The authors would like to thank all patients and controls for their participation in the present study.

Disclosure statement

The authors report no conflicts of interest.

Additional information

Funding

This study was supported by Cuiying Science and Technology Innovation Project (No: CY2021-BJ-A07), Cuiying Student Project (No: CYXZ2022-51) and Lanzhou Science and Technology Plan Project (NO: 2021-1-104).