title: Tumor-infiltrating PD1-Positive Lymphocytes and FoxP3-Positive Regulatory T Cells Predict Distant Metastatic Relapse and Survival of Clear Cell Renal Cell Carcinoma.
abstract: BACKGROUND
  Clear cell renal cell carcinoma (CRCC) is the most common malignant tumor of the kidney, and the clinical outcome of CRCC is related with the metastatic potential of CRCC. A significant proportion of metastatic CRCC remains incurable. Recently, immunotherapy against specific targets such as programmed death 1 (PD1) has been adapted for fatal cases of CRCC.
  
  
  METHODS
  In this study, we aimed to evaluate the potential of tumor-infiltrating PD1-positive lymphocytes or FoxP3-positive regulatory T cells (Tregs) as predictors of the metastatic potential or prognosis of CRCC and investigate possible correlations with Epstein-Barr virus (EBV) infection in 199 cases of CRCC.
  
  
  RESULTS
  PD1 positivity, high Treg number, and EBV infection all predicted poor overall survival (OS) by univariate analysis. PD1 positivity and high Treg numbers were also significantly correlated with more distant metastatic relapse (DMR) and poor relapse-free survival (RFS) by univariate analysis. PD1 positivity and high Treg number were independent prognostic indicators for OS. In addition, PD1 positivity was an independent predictor of RFS and DMR. EBV infection was an independent predictor of OS of CRCC.
  
  
  CONCLUSIONS
  This study demonstrates that intratumoral infiltration of PD1-positive or FoxP3-positive lymphocytes can be used as significant prognostic indicators of CRCC and PD1 positivity could be very helpful in the prediction of latent distant metastasis of CRCCs. Therefore, evaluation of the infiltration of PD-positive cells or Tregs in CRCC may be useful diagnostic tools for the selection of patients who could benefit from PD1- or Treg-based immunotherapy.
authors.affiliation: Department of Pathology, Chonbuk National University Medical School, Research Institute of Clinical Medicine and Institute for Medical Sciences, Jeonju, Jeonbuk, Republic of Korea.
authors.forename: Myoung Jae
authors.initials: MJ
authors.lastname: Kang
authors.forename: Kyoung Min
authors.initials: KM
authors.lastname: Kim
authors.forename: Jun Sang
authors.initials: JS
authors.lastname: Bae
authors.forename: Ho Sung
authors.initials: HS
authors.lastname: Park
authors.forename: Ho
authors.initials: H
authors.lastname: Lee
authors.forename: Myoung Ja
authors.initials: MJ
authors.lastname: Chung
authors.forename: Woo Sung
authors.initials: WS
authors.lastname: Moon
authors.forename: Dong Geun
authors.initials: DG
authors.lastname: Lee
authors.forename: Kyu Yun
authors.initials: KY
authors.lastname: Jang