title: Infiltrating memory/senescent T cell ratio predicts extrahepatic metastasis of hepatocellular carcinoma.
abstract: BACKGROUND
  The density of tumor-infiltrating immunocytes (TICs) has been proposed as an independent predictor of intrahepatic recurrence in patients with hepatocellular carcinoma (HCC). However, the relative roles of TIC density in predicting tumor extrahepatic metastasis remain to be elucidated.
  
  
  METHODS
  The densities of CD3(+), CD8(+), granzyme B(+), FoxP3(+), CD45RO(+), CD20(+), CD1a(+), CD83(+), CD57(+), and CD68(+) TICs were assessed by immunohistochemistry in tissue microarrays containing paired intratumoral (IT) and peritumoral (PT) tissues from 206 consecutive HCC patients who underwent liver transplantation. Occurrence of extrahepatic metastasis, recurrence-free survival (RFS), and cancer-specific survival (CSS) were assessed retrospectively in relation to TIC densities.
  
  
  RESULTS
  CD45RO(+) memory T cell density was lower in tumor tissue compared with peritumor, whereas CD57(+) senescent T cell density was higher. Univariate analysis revealed that increased CD45RO (IT) (+) and decreased CD57 (PT) (+) densities were statistically significantly associated with favorable RFS and CSS, while other types of TICs, intratumorally or peritumorally, showed no prognostic values. Further, the CD45RO (IT) (+) /CD57 (PT) (+) ratio could stratify patients more accurately in terms of RFS and CSS than either marker used alone. Finally, multivariate analysis indicated that a high CD45RO (IT) (+) /CD57 (PT) (+) ratio was independently associated with better RFS (hazard ratio [HR] = 0.64; 95% confidence interval [CI], 0.42 to 0.98; P = 0.040) and CSS (HR = 0.51; 95% CI, 0.31 to 0.83; P = 0.007), but not CD45RO (IT) (+) or CD57 (PT) (+) individually.
  
  
  CONCLUSIONS
  These results suggest that the CD45RO (IT) (+) /CD57 (PT) (+) (memory/senescent T cell) ratio is of vital importance in preventing HCC extrahepatic metastasis and in particular demonstrates its independent prognostic value in liver transplant recipients.
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital and Shanghai Medical School, Fudan University, Shanghai, People's Republic of China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Gao
authors.forename: Jian
authors.initials: J
authors.lastname: Zhou
authors.forename: Xiao-Ying
authors.initials: XY
authors.lastname: Wang
authors.forename: Shuang-Jian
authors.initials: SJ
authors.lastname: Qiu
authors.forename: Kang
authors.initials: K
authors.lastname: Song
authors.forename: Xiao-Wu
authors.initials: XW
authors.lastname: Huang
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.forename: Ying-Hong
authors.initials: YH
authors.lastname: Shi
authors.forename: Bai-Zhou
authors.initials: BZ
authors.lastname: Li
authors.forename: Yong-Sheng
authors.initials: YS
authors.lastname: Xiao
authors.forename: Jia
authors.initials: J
authors.lastname: Fan
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000276:immunology* / Q000401:mortality / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D008113:Liver Neoplasms / Q000276:immunology* / Q000401:mortality / Q000473:pathology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000276:immunology / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology