Expression of the immune checkpoint CD137/CD137L in oral squamous cell carcinoma (OSCC) and association with histopathological parameters.

Abstract

As immunotherapy (IT) with checkpoint inhibitors continues to make rapid progress in the treatment of oral squamous cell carcinoma (OSCC), response rates still necessitate substantial improvement. Current concepts to improve therapy response mainly consider identification of further immunological targets eligible for extension of IT. One auspicious immune checkpoint is CD137 and its ligand CD137L, but expression rates and relevance for progression of OSCC are still unknown. Tissue and peripheral blood from 159 OSCC patients and 55 healthy oral mucosa (HOM) controls was collected and subsequently analyzed for expression of CD137 and CD137L by quantitative reverse transcription polymerase chain reaction (RT-qPCR). Furthermore, OSCC and HOM tissue samples from both groups were evaluated for CD137 protein expression by immunohistochemistry (IHC). Expression rates were analyzed and subsequently correlated with histomorphological characteristics. CD137 exhibited highly significant upregulation in OSCC tissue on mRNA and protein level, as evidenced by both RT-qPCR (p < 0.001) and IHC (p < 0.001) analysis. Regarding the CD137L expression in the examined tissue specimens, there was no significant difference detectable on mRNA level (p = 0.53). Comparative analysis of RT-qPCR blood data showed no statistically significance in expression rates of CD137 (p = 0.653) and CD137L (p = 0.351). Correlation analysis revealed no highly significant results with reference to the histopathological parameters. CD137 showed a highly significant upregulation in OSCC tissue compared to the HOM control group. Consequently, it may be a relevant checkpoint involved into formation and progression of OSCC. Further investigations are needed to evaluate, if CD137 represents a suitable target for a novel IT approach in OSCC treatment.