PD-1 expression on peripheral blood cells increases with stage in renal cell carcinoma patients and is rapidly reduced after surgical tumor resection (TUM2P.881)

In this study, we analyzed expression of numerous immune cell markers on fresh PBMC from 90 RCC patients preoperatively and 25 age-matched healthy controls by 10-color flow cytometry. Postoperative blood samples were also analyzed from 23 members of the RCC patient cohort. The most striking phenotypic immune biomarker in RCC patients was a significant increase in PD-1 expression on certain PBMC in a subset of patients. Increased PD-1 expression on CD14bright myelomonocytic cells, effector T cells, and NK cells correlated to disease stage. Importantly, we also observed that expression was significantly reduced on all cell types in virtually all patients within 2 weeks after surgical resection of the primary tumor. Based upon our results, we conclude that PD-1 expression on fresh peripheral blood leukocytes may provide a useful indicator of RCC disease progression. Furthermore, measuring PD-1 levels in peripheral blood may assist in identifying patients likely to respond to PD-1 blocking antibodies, and these therapies may be most effective before and immediately after surgical resection of the primary tumor, when PD-1 expression is most prominent. Finally, we conclude that long-term PD-1 blocking therapy after nephrectomy may only be effective in stage 3 and stage 4 patients that retain PD-1 expression, presumably maintained by the presence of residual metastatic tumor.