Washington, DC (UroToday.com): Monocytes are an important component of innate and adaptive immunity due to their ability to phagocytose, produce cytokines, and present antigens. They are characterized into three different subsets based on cell-surface markers—classical monocytes (CM), intermediate monocytes, and nonclassical monocytes. Classical monocytes constitute up to 95% of all monocytes. Monocytes migrate into tissue and are then called macrophages.
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PD-1 is an inhibitory checkpoint receptor expressed on lymphocytes and antigen-presenting cells, including monocytes. RCC cells can produce PD-L1 ligand and inhibit anti-tumor immunity via interaction with PD-1. The group from Fox Chase Cancer Center has previously showed that peripheral blood lymphocyte PD-1 expression is elevated among newly diagnosed RCC patients compared to age-matched healthy controls. Additionally, PD-1 levels are decreased post-operatively across all peripheral blood lymphocytes. The group now theorized whether classical monocyte inhibition through PD-1 interferes with antigen presentation and is prognostic of poor survival outcomes.
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 % cells that express a biomarker. Patients were excluded if they had comorbid CLL, prior surgeries for RCC, non-clear cell RCC histology, or if the FC data was missing. The group defined elevated CM PD-1 level at the third quartile of CM PD-1 expression (784 MFI) in the healthy donors. Cancer specific survival (CSS) curves were estimated with Kaplan-Meier methods and Cox proportional hazards models were used to estimate adjusted hazard ratios.
68 patients with clear cell RCC were included with average age 60 (range 25-88) years. With median follow-up of 41 months (range 1-55 months), 10 patients died with ccRCC. Median CM (%) was lower in those who died of disease compared to censored (64% vs 52%, p=0.029) even though median monocyte count was similar (median 650 cells/μl vs 550 cells/μl, p = 0.179). Patients with CM PD-1 expression > 784 had lower cancer CSS compared to patients with CM PD-1 expression < 784 (p = 0.017). In a multivariate analysis adjusted for stage-related variables, CM PD-1 MFI> 784 was associated with inferior CSS (HR 8.6 [95% CI 1.4-51], p = 0.018) while higher CM% was associated with improved CSS ( HR 0.69 [95% CI 0.47-0.99], p = 0.046).
The group concludes that an elevated preoperative CM PD-1 level and lower CM% was associated with poor survival. Preoperative CM PD-1 and CM% may be important biomarkers to stratify patients at risk for poor outcomes who may benefit from immunotherapy.
Mohammed Haseebuddin, MD. from the 2015 Winter Meeting of the Society of Urologic Oncology (SUO) "Defining Excellence in Urologic Oncology" - December 2 - 4 Washington, DC.
Fox Chase Cancer Center, Philadelphia, PA.