103 Background: Glioma is a highly lethal tumor that is known for its immune inhibitory capabilities. Despite great progress in treatment modalities, the median survival time of high-grade gliomas patients is only about 11.1 months. Gliomas are aberrantly expressed programmed death–ligand 1 (PD-L1) which results in tumor-induced immune suppression. Hypoxia is well known to induce aggressiveness, promotes tumor progression and resistance to chemotherapy and radiotherapy. Recently, studies have indicated that hypoxia play a prominent role in tumor immune escape. The aim of the study was to explore the relationship between PD-L1 and hypoxia inducible factor 1α (HIF-1α) and the role in the progression of gliomas. Methods: We adopted immunohistochemistry methods to detect expressions of PD-L1 and HIF-1α in 64 surgical specimens (23 cases for low-grade and 41 cases for high-grade gliomas, respectively). Immunoreactivity was analyzed in association with patients’ clinical characteristics or survival time. Expression of the PD-L1 and HIF-1α was analyzed in three GBM cell lines, U343, U373, and U251, under in vitro hypoxia (12, 24 or 72 h at 0.1% O2). Reverse transcriptase-polymerase chain reaction (RT-PCR) was carried out to detect the mRNA expression of PD-L1 and HIF-1α. Results: PD-L1 and HIF-1α protein expression was detected in 81.25% and 84.73% of glioma specimens, respectively. The expression of PD-L1 protein is positively correlated with HIF-1α (r = 0.52; p= 0.013). Kaplan–Meier analysis revealed a significant effect of PD-L1 grade on cumulative overall survival. Patients with negative PD-L1 expression survive longer than those with positive expression ( p= 0.007). PD-L1 and HIF-1α mRNA was most consistently upregulated in relation to duration of in-vitro hypoxia (72h, p= 0.007). There was a significant and positive relationship between the PD-L1 and HIF-1α mRNA expression (r = 0.45; p= 0.01). Conclusions: The present study showed a role for hypoxia/HIF-1α in driving immune escape and provided a potential novel cancer immunotherapy targeting hypoxia to block PD-L1 expression, which may boost the immune system in cancer patients.
Upregulation of hypoxia-inducible factor 1α mRNA expression was associated with poor prognosis in patients with hepatocellular carcinoma