title: Overexpression of PD-L1 significantly associates with tumor aggressiveness and postoperative recurrence in human hepatocellular carcinoma.
abstract: OBJECTIVE
  The aberrant expression of programmed cell death 1 ligands 1 and 2 (PD-Ls) on tumor cells dampens antitumor immunity, resulting in tumor immune evasion. In this study, we investigated the expression of PD-Ls in human hepatocellular carcinoma (HCC) to define their prognostic significance after curative surgery.
  
  
  METHODS
  Immunohistochemistry was used to investigate PD-Ls expression as well as granzyme B+ cytotoxic and FoxP3+ regulatory T cell infiltration on tissue microarrays containing 240 randomly selected HCC patients who underwent surgery. The results were further verified in an independent cohort of 125 HCC patients. PD-Ls expression on HCC cell lines was detected by Western blot assay.
  
  
  RESULTS
  Patients with higher expression of PD-L1 had a significantly poorer prognosis than patients with lower expression. Although patients with higher expression of PD-L2 also had a poorer survival, the difference in recurrence was not statistically significant. Multivariate analysis identified tumor expression of PD-L1 as an independent predictor for postoperative recurrence. No correlation was found between PD-Ls expression and granzyme B+ lymphocyte infiltration, whereas a significant positive correlation was detected between PD-Ls expression and FoxP3+ lymphocyte infiltration. In addition, tumor-infiltrating cytotoxic and regulatory T cells were also independent prognosticators for both survival and recurrence. The prognostic value of PD-L1 expression was validated in the independent data set.
  
  
  CONCLUSIONS
  Our data suggest for the first time that PD-L1 status may be a new predictor of recurrence for HCC patients and provide the rationale for developing a novel therapy of targeting the PD-L1/PD-1 pathway against this fatal malignancy.
authors.affiliation: Liver Cancer Institute, Zhong Shan Hospital and Shanghai Medical School, Shanghai, People's Republic of China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Gao
authors.forename: Xiao-Ying
authors.initials: XY
authors.lastname: Wang
authors.forename: Shuang-Jian
authors.initials: SJ
authors.lastname: Qiu
authors.forename: Ichiro
authors.initials: I
authors.lastname: Yamato
authors.forename: Masayuki
authors.initials: M
authors.lastname: Sho
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Nakajima
authors.forename: Jian
authors.initials: J
authors.lastname: Zhou
authors.forename: Bai-Zhou
authors.initials: BZ
authors.lastname: Li
authors.forename: Ying-Hong
authors.initials: YH
authors.lastname: Shi
authors.forename: Yong-Sheng
authors.initials: YS
authors.lastname: Xiao
authors.forename: Yang
authors.initials: Y
authors.lastname: Xu
authors.forename: Jia
authors.initials: J
authors.lastname: Fan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism*; D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D045744:Cell Line, Tumor; D018450:Disease Progression; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012008:Recurrence
chemical_list: D015703:Antigens, CD; D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human