Soluble forms of the immune check-point receptor PD-1 and its ligand PD-L1 in blood serum of patients with renal cell carcinoma: clinical and pathologic correlations

Background.Renal cancer is one of the most immunosensitive oncologic diseases. A prominent breakthrough in this field was gained with the development of medications directed to the suppression of PD-1/PD-L immune check-point signaling pathway that in normal physiologic conditions controls autoimmune reactions. Tumor PD-1 and/or PD-L1 expression is investigated both as a predictor of corresponding immunotherapy efficiency, and as molecular markers of overall prognosis and patients’ survival. This goal could be also attained by the measure­ment of soluble forms of these proteins (sPD-1 иsPD-L1) in blood serum.

Objective of the study— comparative evaluation ofsPD-1 and sPD-L1 content in blood serum of practically healthy persons and patients with renal cancer and benign kidney tumors; analysis of the associations between these markers and clinical and pathologic characteristics of renal cancer.

Materials and methods. 106 renal cancer (64 male and 42 female; age 33—81 years) and 11 patients with benign kidney tumors (3 male and 8 female; age 29—84 years) were included in the study. Control group comprised 19 men and 18 women of matching age. 57patients had stage I, 12 — II, 15 — III and 22 — stage IVrenal cancer. Serum sPD-L1 and sPD-1 concentrations were measured using standard enzyme immunoassay kits (Affimetrix, eBioscience, USA).

Results. sPD-L1 levels in blood serum of patients with primary renal cancer and benign tumors were significantly higher than in control (p <0.0001 and p <0.05 respectively). sPD-L1 level significantly increased with disease stage (p <0.001), with T index increase from 1 to 3 declining at T4, was significantly higher in patients with lymph node metastases (both N1, and N2) than in those without such lesions (N0); it was also increased in М+ patients, and in patients with grade III—IVin comparison to grade I—II tumors. sPD-1 levels did not differ sig­nificantly between study groups, did not depend on disease stage, presence of lymph node or distant metastases, but were decreased in patients with Т4 as compared to those with less advanced primary tumor, and were significantly lower in patients with clear-cell than in those with chromophobic or papillary histologic variants.

Conclusion. Serum sPD-L1 in renal cancer patients correlates with disease progression and tumor grade, and can be regarded as promising marker for monitoring of anti-PD1/PD-L1 treatment efficiency. Potential clinical implications of sPD-1 require further investigations and analysis.