PD-1/PD-L1 expression in chromophobe renal cell carcinoma: An immunological exception?

Immune checkpoint inhibitors targeting the inhibitory cross talk between tumor and immune cells have been approved for therapy in renal cell carcinoma (RCC). In contrast to clear cell RCC, little is known on PD-1/PD-L1 expression patterns in rarer RCC subtypes. The aim of this study was to evaluate the prevalence, distribution and prognostic impact of PD-1 and PD-L1 expression in chromophobe (ch)RCC. Patients who underwent renal surgery due to chRCC were retrospectively evaluated. Tumor specimen was analyzed for PD-1 and PD-L1 expression by immunohistochemistry. Expression data were correlated with clinic-pathological parameters including patient survival. Eighty-one chRCC patients were eligible for analysis, thereof 25 (30.9 %) and 11 (13.6 %) patients were positive for PD-1⁺ tumor-infiltrating mononuclear cells (TIMCs) and tumoral PD-L1⁺ expression, respectively. No significant associations were found for PD-1⁺ TIMC or tumoral PD-L1⁺ expression and clinical attributes. In addition, no differences in 5- and 10-year overall survival for PD-1^- TIMC compared to PD-1⁺ TIMC (90.5 and 72.2 vs. 100 and 75 %; p = 0.41) and for PD-L1^- tumors compared to PD-L1⁺ tumors (91.9 and 76.4 vs. 100 and 50 %; p = 0.48) were observed. In conclusion, to our knowledge this is the first study to evaluate the prognostic impact of PD-1 and PD-L1 in chRCC. PD-L1 does seem to be expressed in a minority of all chRCC, likewise only a minority of chRCC was infiltrated by PD-1-positive inflammatory cells. Neither PD-1⁺ TIMC nor tumoral PD-L1⁺ expression was associated with parameters of aggressiveness or survival.