PD-1 expression on classical monocytes (CM) as an independent predictor of cancer specific survival in clear cell renal carcinoma (ccRCC).

Abstract

562 Background: We have previously shown that PD-1 expression in peripheral blood lymphocytes is elevated in RCC patients at diagnosis and decreases subsequent to surgery. We theorize that classical monocyte (CM) inhibition through PD-1 interferes with antigen presentation necessary to stimulate adaptive immune responses, and, thus, preop CM PD-1 expression is prognostic of poor outcomes. Methods: Blood samples were obtained from RCC patients (n = 90) preop and age-matched healthy donors (n = 25). Flow cytometric (FC) data were quantified as mean fluorescence intensity (MFI) or % of cells that express a biomarker. Patients were excluded if they had comorbid CLL, had prior surgeries for RCC, had non-ccRCC histology, or if the FC data was missing. We have defined elevated CM PD-1 expression at the third quartile level of CM PD-1 expression (784 MFI) in the healthy donors. CM PD-1 level was correlated with patient clinico-pathologic data using non-parametric tests. Cancer specific survival (CSS) curves were estimated with Kaplan-Meier methods and a multivariate analysis was performed. Results: The average age of the ccRCC cohort (n = 68) was 60 (range 25-88) years. 35 patients were Fuhrman Grade III/IV high-grade (HG) histology. With median follow-up of 41 months, 10 patients died with ccRCC. No patients with low-grade disease died. Median CM (%) was lower in those who died of disease compare to censored (64% vs 52%, p = 0.029). Patients with CM PD-1 expression > 784 MFI had lower survival compared to patients with CM PD-1 < 784 MFI (p = 0.02). Among HG patients, CSS at 24 months for CM PD-1 MFI > 784 was 62.1% (95% CI 34.2-81.0) vs 93.3% (95% CI 61.3-99.0) for CM PD-1 MFI < 784. On multivariable analysis, controlling for stage related covariates, CM PD-1 MFI > 784 is associated with inferior CSS (hazard ratio = 5.1 [95% CI: 1.1-24.4], p = 0.04) among HG disease patients. Conclusions: In patients with ccRCC, an elevated preoperative CM PD-1 MFI level was associated with lower survival independent of pathological T stage and localized disease status. Preoperative CM PD-1 MFI may be an important biomarker to stratify patients at risk for poor outcome who may benefit from immunotherapy.