title: Quantitative effect of natural killer-cell licensing on hepatocellular carcinoma recurrence after curative hepatectomy.
abstract: Natural killer (NK) cells have a potential role in immune surveillance of hepatocellular carcinoma (HCC). Self-recognition of human leukocyte antigens (HLA) through killer immunoglobulin-like receptors (KIR) confers competence to NK cells-a process termed "licensing." We investigated the effect of NK-cell licensing on the susceptibility of patients to HCC recurrence. A total of 170 Japanese patients with HCC who underwent primary curative hepatectomy between 1996 and 2010 were enrolled in this study. The median follow-up period was 5.4 years. We analyzed their KIR-HLA genotypes with sequence-specific polymorphism-based typing and estimated their susceptibility to HCC recurrence by performing propensity score-matching analyses. The presence of KIR2DL1-C2, KIR2DL2-C1, KIR3DL1-BW4, or KIR3DL2-A3/11, functional compound genotypes that intrinsically license NK cells, did not markedly affect HCC recurrence. However, the multiplicity of those compound KIR-HLA genotypes was significantly associated with the HCC recurrence rate, i.e., the cumulative risk of recurrence in patients with at least three compound genotypes was significantly lower than that in patients with one or two compound genotypes, suggesting that the effect of NK-cell licensing on HCC recurrence is quantitative. Patients at high risk of HCC recurrence after curative hepatectomy could be identified by KIR-HLA genotyping.
authors.affiliation: Gastroenterological and Transplant Surgery, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan. Liver Research Project Center, Hiroshima University, Hiroshima, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Tanimine
authors.affiliation: Gastroenterological and Transplant Surgery, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan. Liver Research Project Center, Hiroshima University, Hiroshima, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Gastroenterological and Transplant Surgery, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan. Liver Research Project Center, Hiroshima University, Hiroshima, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Gastroenterological and Transplant Surgery, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan. Liver Research Project Center, Hiroshima University, Hiroshima, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Tashiro
authors.affiliation: Liver Research Project Center, Hiroshima University, Hiroshima, Japan. Laboratory for liver Disease, RIKEN Center for Genomic Medicine, Hiroshima, Japan.
authors.forename: Daiki
authors.initials: D
authors.lastname: Miki
authors.affiliation: Liver Research Project Center, Hiroshima University, Hiroshima, Japan. Medicine and Molecular Science, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Michio
authors.initials: M
authors.lastname: Imamura
authors.affiliation: Liver Research Project Center, Hiroshima University, Hiroshima, Japan. Medicine and Molecular Science, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Aikata
authors.affiliation: Liver Research Project Center, Hiroshima University, Hiroshima, Japan. Epidemiology, Infectious Disease Control and Prevention, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Tanaka
authors.affiliation: Liver Research Project Center, Hiroshima University, Hiroshima, Japan. Laboratory for liver Disease, RIKEN Center for Genomic Medicine, Hiroshima, Japan. Medicine and Molecular Science, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chayama
authors.affiliation: Gastroenterological and Transplant Surgery, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan. Liver Research Project Center, Hiroshima University, Hiroshima, Japan. hohdan@hiroshima-u.ac.jp.
authors.forename: Hideki
authors.initials: H
authors.lastname: Ohdan
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000276:immunology* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006498:Hepatectomy; D006649:Histocompatibility Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics / Q000276:immunology* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D054340:Receptors, KIR / Q000235:genetics; D047368:Tumor Burden
chemical_list: D006649:Histocompatibility Antigens; D054340:Receptors, KIR