Introduction & Objectives: Immune checkpoint proteins are recognized as critical regulators of the immune system and play an important role in the defence against cancer. Unfortunately, cancer cells evade the immune destruction by overexpressing inhibitory checkpoint proteins, hence creating a favourable tumour microenvironment. Recently, it has been proposed that immune checkpoint proteins can be detected in soluble form in body fluids. This is important since a blood sample is less invasive than a tissue sample and hypotheticall yhas the potential to be more representative. The aim of the study was to evaluate the concentrations of soluble immune inhibitory checkpoint proteins (sICs) in men with and without penile cancer.
Materials & Methods: The circulating levels of ten soluble immune inhibitory checkpoint proteins (TIM-3, CD152, HVEM, IDO, LAG-3, BTLA, CD80, PD-1, PD-L1 and PD-L2) were assessed in plasma of 206 men with penile cancer (cases) and 46 men free from penile cancer (controls) using a multiplex Luminex assay. Mean concentrations of sICs were calculated and bootstrap resampling together with Welch's t-tests were used to assess differential expression and distribution of sICs between cases and controls.
Results: HVEM was detectable in 87% of the samples. PD-L1 was only detectable in 43.3% and therefore excluded from further analyses. The remaining markers were detectable in all samples. When comparing the mean concentrations of soluble immune inhibitory checkpoint proteins, nine sICs were found in higher concentrations in cases compared to controls, out of which seven reached statistical significance (Table 1).
Conclusions: Our study indicates that men with penile cancer have higher concentrations of soluble immune inhibitory checkpoint proteins in plasma compared to penile cancer-free men. Further studies are needed to evaluate their prognostic value