Abstract
Regulation of immunity is a unique oncogenic mechanism that differs in different cancers. VHL deficient clear cell renal cell carcinomas (ccRCC) trigger the immune response resulting in cancer progression. This study aimed to investigate PD-1, PD-L1, and PD-L2 expression in ccRCC primary cancers and metastatic tissues associated with the p-VHL content, transcriptional, and growth factors expression. Methods: A total of 62 patients with RCC were enrolled in the study. Investigation of mRNA level was performed by PCR in real-time. Western blotting analysis was used for detecting the p-VHL protein content in tissues. Results: The PD-L2 prevalence in metastatic cancers is crucial in tumor progression. The VHL expression and p-VHL content determined the aggressive cancer behavior and elevated in disseminated tumors. The cancer dissemination was accompanied by an increase in both mRNA and VHL content. Conclusion: We present a new instrument targeting pathologies with p-VHL/HIF altered function that impact the PD-L2 expression through the change in transcriptional, growth factors, and AKT/mTOR modulation.
Highlights
Tumor immunogenicity is one of the urgent problems in modern oncology
Under physiological conditions, when PD-1 interacts with its ligands (PD-L1, PD-L2), an inhibitory signal is transmitted that prevents the development of an excessive immune response, triggering the processes of apoptosis of cytotoxic lymphocytes [2]
A 2.69-fold decrease in the PD-L2 mRNA level in metastases was recorded compared to the primary tumor tissue
Summary
Tumor immunogenicity is one of the urgent problems in modern oncology. Receptor PD-1 (Programmed cell death 1; CD279) plays a role in the cellular differentiation of immune cells [1]. Under physiological conditions, when PD-1 interacts with its ligands (PD-L1, PD-L2), an inhibitory signal is transmitted that prevents the development of an excessive immune response, triggering the processes of apoptosis of cytotoxic lymphocytes [2]. The recent analysis highlights the VHL impact on the biological processes, including metabolism, immune regulation, apoptosis, and cell movement. Its overexpression promotes immune system activation and sensitivity to interferon therapy [3]. The studies showed that PD-L1 expression levels positively correlate with VHL mutation and HIF-2α expression. VHL mutations positively correlate with PD-L1 expression in ccRCC and may influence ccRCC anti-PD-L1/PD-1 immunotherapy [4]
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