title: Natural Killer Lymphocytes Are Dysfunctional in Kidney Transplant Recipients on Diagnosis of Cancer.
abstract: BACKGROUND
  The incidence of cancer is increased after solid organ transplantation. Natural killer (NK) cells are key effectors of the tumor immune response.
  
  
  METHODS
  We conducted a cross sectional multicentre matched case-control study including 42 kidney transplant recipients (KTRs) on diagnosis of cancer and 41 KTRs without cancer. Extensive phenotyping of NK cells populations and functional tests of NK cells were performed.
  
  
  RESULTS
  Kidney transplant recipients with cancer had a higher incidence of acute rejection (P = 0.02) and cytomegalovirus (CMV) infection (P = 0.03) than controls. They had more lymphopenia than control KTRs (1020/mm3 +/- 32 vs 1218/mm3 +/- 34; P = 0.001) including a CD4+ lymphopenia (P = 0.01). Total CD3-/CD56+ NK cell counts were similar in both groups. However, KTRs with cancer had a lower frequency of the cytokine-enriched CD56bright NK cell subset (P = 0.001). The percentage of NK cells expressing NKp46 was decreased in KTRs with cancer (45% vs 53 %, P = 0.001). Furthermore, the ability of NK cells to degranulate CD107a+ cytolytic vesicles was reduced (11% vs 22%; P = 0.02), and the percentage of NK cells secreting IFN[gamma] was decreased (7.5% vs 28.8%; P = 0.01) in KTRs with cancer.
  
  
  CONCLUSIONS
  These results reveal an imbalance between NK cell subpopulations and functional NK cell defects in KTRs at the diagnosis of malignancy, including a decreased expression of NKp46 and decreased numbers of NK cells producing INF[gamma]. This study highlights the role of NKp46, a major activating NK cell receptor, which could be considered as a potential marker during immunological follow-up of KTRs.
authors.forename: Marie-Noëlle
authors.initials: MN
authors.lastname: Peraldi
authors.forename: Jeannig
authors.initials: J
authors.lastname: Berrou
authors.forename: Marion
authors.initials: M
authors.lastname: Venot
authors.forename: Victor
authors.initials: V
authors.lastname: Chardiny
authors.forename: Antoine
authors.initials: A
authors.lastname: Durrbach
authors.forename: Vincent
authors.initials: V
authors.lastname: Vieillard
authors.forename: Patrice
authors.initials: P
authors.lastname: Debré
authors.forename: Dominique
authors.initials: D
authors.lastname: Charron
authors.forename: Caroline
authors.initials: C
authors.lastname: Suberbielle
authors.forename: Sylvie
authors.initials: S
authors.lastname: Chevret
authors.forename: Denis
authors.initials: D
authors.lastname: Glotz
authors.forename: Nicolas
authors.initials: N
authors.lastname: Dulphy
authors.forename: Antoine
authors.initials: A
authors.lastname: Toubert
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D019002:CD56 Antigen / Q000378:metabolism; D016022:Case-Control Studies; D002478:Cells, Cultured; D003430:Cross-Sectional Studies; D003586:Cytomegalovirus Infections / Q000453:epidemiology / Q000276:immunology; D005260:Female; D006084:Graft Rejection / Q000453:epidemiology / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D015994:Incidence; D007371:Interferon-gamma / Q000378:metabolism; D016030:Kidney Transplantation / Q000009:adverse effects*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D016131:Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D008231:Lymphopenia / Q000453:epidemiology / Q000276:immunology; D008297:Male; D008875:Middle Aged; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000378:metabolism; D009369:Neoplasms / Q000453:epidemiology / Q000276:immunology* / Q000378:metabolism; D010297:Paris / Q000453:epidemiology; D010641:Phenotype; D012307:Risk Factors; D066027:Transplant Recipients; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D019002:CD56 Antigen; C573415:IFNG protein, human; C522918:NCAM1 protein, human; C112260:NCR1 protein, human; D055627:Natural Cytotoxicity Triggering Receptor 1; D007371:Interferon-gamma