Prognostic significance of sPD-1/sPD-L1 in renal cancer depending on the phenotype of tumor and stromal cells

Abstract

Background. The search for new prognostic markers of renal cell carcinoma is an urgent problem of oncourology. Modern studies demonstrate the need for a comprehensive assessment of the clinical and prognostic significance of many markers.Aim is a comprehensive analysis of the prognostic significance of soluble forms of PD-1 and PD-L1 (sPD-1 and sPD-L1) depending on the phenotype of tumor cells and the microenvironment.Materials and methods. The study included tumor tissue and serum samples from 54 patients with renal cell cancer and from 67 healthy donors. The concentrations of sPD-1 and sPD-L1 were determined in blood serum using ELISA. Tissue expression of PD-L1, PU.1, CD3, and CD20 was assessed by immunohistochemistry. To determine statistically significant differences in independent groups, the Mann–Whitney test and Fisher’s exact test were used. Overall survival was analyzed by constructing survival curves using the Kaplan–Meier method. Differences were considered statistically significant at p <0.05.Results. Increase of sPD-L1 concentration in serum from patients with renal cell carcinoma compared with healthy donors was demonstrated. The highest concentration of the soluble form of the PD-1 receptor was observed in serum from patients with the non-clear cell renal cell carcinoma. High levels of sPD-L1 in serum and PD-L1 in tumor cells are associated with disease progression (advanced stage, higher malignancy, as well as the presence of regional metastases). It has been shown that the high content of PU.1+ and CD20+ cells in the tumor stroma are significant factors of unfavorable prognosis. No prognostic significance was found for both sPD-L1 and PD-L1 expressed in tumor tissue. However, analysis of a combination of these markers showed that the high concentration of sPD-L1 together with the high tissue expression of PD-L1 is an extremely unfavorable factor.Conclusion. Analysis of sPD-L1 concentration and tissue expression of PD-L1 in combination is a new approach for assessing the prognosis of renal cell carcinoma.