Impact of tumor-infiltrating immune cells expressing PD-1 and those expressing PD-L1 on recurrence and prognosis in pathological T1b clear cell renal cell carcinoma.

Background: The numbers of tumor-infiltrating immune cells (TIICs) expressing programmed death (PD)-1 or PD-ligand 1 (PD-L1) reportedly predict prognosis and resistance to targeted drugs in clear cell renal cell carcinoma (ccRCC). The impact of local tumor microenvironment based on immunosuppressive TIICs on recurrence and prognosis has not been fully investigated in localized ccRCC.

Methods: A total of 105 patients with pT1b ccRCC were included. Immunostaining for PD-1 and PD-L1 were performed. PD-1-positive TIICs and PD-L1-positive TIICs were counted in the tumor periphery (TP) and the tumor nest (TN).

Results: Patients with elevated PD-1-positive TIIC scores and those with elevated PD-L1-positive TIIC scores had significantly lower recurrence-free survival (RFS) rates than their counterparts (3-year RFS rates; patients with high vs. low PD-1-positive TIIC score of TN = 73.9% vs. 95.0%, those with high vs. low PD-1-positive TIIC score of TP = 73.8% vs. 93.8%, those with high vs. low PD-L1-positive TIIC score of TN = 70.9% vs. 93.0%, and those with high vs. low PD-L1-positive TIIC score of TP = 80.3% vs. 92.6%). Univariate analysis showed that high PD-1-positive scores, high PD-L1-positive scores, high PD-L1-positive tumor cell score, high-grade tumor, tumor necrosis, and lymphovascular invasion were significantly associated with RFS. Multivariate analysis revealed that tumor necrosis [hazard ratio (HR) = 2.841, P = .0269] and PD-1-positive TIIC score of TN (HR = 6.135, P = .0023) were independent risk factors for RFS. Risk stratification using the two factors efficiently predicts recurrence (3-year RFS rates: 96.4% with 0 factor, 83.8% with 1 factor, and 61.4% with 2 factors).

Conclusion: PD-1-positive TIIC score of TN and tumor necrosis may efficiently predict recurrence in pT1b ccRCC.