Soluble PD-L1 is a promising disease biomarker but does not reflect tissue expression in classic Hodgkin lymphoma.

Individually, tissue and soluble markers involved in the programmed cell death protein 1/programmed death-ligand (PD-1/PD-L) axis have been described as biomarkers with clinical value in classical Hodgkin lymphoma (cHL). In the context of the success of immune checkpoint blockade therapy in cHL, it is interesting to discover whether plasma levels of proteins in the PD-1/PD-L axis are a reflection of expression by the corresponding tissue. Paired tissue and plasma samples of cHL patients were collected and analysed for PD-1, PD-L1 and PD-L2 levels. In addition, vascular endothelial growth factor (VEGF) and CD83, molecules regarded to influence the expression of PD-1, PD-L1 and/or PD-L2, were included. PD-L1 was upregulated in the plasma of cHL patients compared to healthy controls and correlated well with several clinical parameters. Strong PD-L1 expression in the tumour microenvironment contributed to high soluble (s)PD-L1 levels, although there was no direct correlation between plasma PD-L1 levels and total expression of PD-L1 in corresponding cHL tissue. Interestingly, we observed a positive correlation between VEGF and PD-1 levels in both tissue and plasma. In conclusion, although PD-L1 is a promising soluble biomarker in cHL, its levels do not reflect the total tissue expression. Future studies focusing on PD-L1 as a predictor for immune checkpoint treatment response, should include both biopsy and plasma samples.

Biomarkers for evaluation of treatment response in classical Hodgkin lymphoma: comparison of sGalectin-1, sCD163 and sCD30 with TARC.

Soluble Galectin-1 (sGal-1, also termed LGALS1), soluble CD163 (sCD163) and soluble CD30 (sCD30) have been reported to be elevated in plasma or serum of patients with classical Hodgkin lymphoma (cHL). We aimed to determine the clinical utility of these biomarkers for evaluation of treatment response compared to thymus and activation regulated chemokine (TARC, also termed CCL17). Plasma or serum samples were prospectively collected among 103 newly diagnosed cHL patients before and after treatment. Levels of sGal-1, sCD163, sCD30 and TARC were correlated with disease characteristics and clinical treatment response. Elevated plasma levels of sGal-1, sCD163, sCD30 and TARC were found in 67%, 21%, 91% and 93% of cHL patients respectively. Mean plasma levels of sGal-1 and sCD30 decreased after treatment but sCD163 did not decrease after treatment. There was no correlation with change of these markers and clinical treatment response in individual patients. TARC levels strongly correlated with disease characteristics and metabolic volume. TARC remained high in 6 out of 7 non-responsive patients and dramatically decreased in 95 out of 96 responsive patients. In summary, elevated pre-treatment levels of sGal-1, sCD163, sCD30 and TARC can be found in patients with cHL. However, only plasma TARC accurately reflects disease activity and correlates with clinical treatment response.