Circular RNA hsa_circ_0000190 Facilitates the Tumorigenesis and Immune Evasion by Upregulating the Expression of Soluble PD-L1 in Non-Small-Cell Lung Cancer

Lung cancer is the leading cause of death from cancer in Taiwan and throughout the world. Immunotherapy has revealed promising and significant efficacy in NSCLC, through immune checkpoint inhibition by blocking programmed cell death protein (PD)-1/PD-1 ligand (PD-L1) signaling pathway to restore patients' T-cell immunity. One novel type of long, non-coding RNAs, circular RNAs (circRNAs), are endogenous, stable, and widely expressed in tissues, saliva, blood, urine, and exosomes. Our previous results revealed that the plasma level of hsa _ circ _ 0000190 can be monitored by liquid-biopsy-based droplet digital PCR and may serve as a valuable blood-based biomarker to monitor the disease progression and the efficacy of immunotherapy. In this study, hsa _ circ _ 0000190 was shown to increase the PD-L1 mRNA-mediated soluble PD-L1 (sPD-L1) expression, consequently interfering with the efficacy of anti-PD-L1 antibody and T-cell activation, which may result in immunotherapy resistance and poor outcome. Our results unraveled that hsa _ circ _ 0000190 facilitated the tumorigenesis and immune evasion of NSCLC by upregulating sPD-L1 expression, potentially developing a different aspect in elucidating the molecular immunopathogenesis of NSCLC. Hsa circ 0000190 upregulation can be an effective indicator for the progression of NSCLC, and hsa _ circ _ 0000190 downregulation may possess a potential therapeutic value for the treatment of NSCLC in combination with immunotherapy.

Automated summary

Lung cancer is the leading cause of death from cancer in Taiwan and worldwide. Immunotherapy has shown promising efficacy in non-small cell lung cancer (NSCLC) by blocking the PD-1/PD-L1 signaling pathway. Circular RNAs (circRNAs) have been identified as potential blood-based biomarkers to monitor the disease progression and immunotherapy efficacy. Hsa_ circ_0000190 was found to interfere with anti-PD-L1 antibody and T-cell activation, leading to immunotherapy resistance and poor prognosis.