title: Expansion of CMV-mediated NKG2C+ NK cells associates with the development of specific de novo malignancies in liver-transplanted patients.
abstract: Solid cancers are a major adverse outcome of orthotopic liver transplantation (OLT). Although the use of chronic immunosuppression is known to play a role in T cell impairment, recent insights into the specificities of NK cells led us to reassess the potential modulation of this innate immune cell compartment after transplantation. Our extensive phenotypic and functional study reveals that the development of specific de novo noncutaneous tumors post-OLT is linked to unusual NK cell subsets with maturation defects and to uncommon cytokine production associated with the development of specific cancers. Remarkably, in CMV(+) patients, the development de novo head/neck or colorectal tumors is linked to an aberrant expansion of NK cells expressing NKG2C and a high level of intracellular TNF-α, which impact on their polyfunctional capacities. In contrast, NK cells from patients diagnosed with genitourinary tumors possessed a standard immature signature, including high expression of NKG2A and a robust production of IFN-γ. Taken together, our results suggest that under an immunosuppressive environment, the interplay between the modulation of NK repertoire and CMV status may greatly hamper the spectrum of immune surveillance and thus favor outgrowth and the development of specific de novo tumors after OLT.
authors.affiliation: INSERM, Unité Mixte de Recherche S945, Laboratoire Immunité et Infections, F-75013 Paris, France;
authors.forename: Abla
authors.initials: A
authors.lastname: Achour
authors.forename: Florence
authors.initials: F
authors.lastname: Baychelier
authors.forename: Caroline
authors.initials: C
authors.lastname: Besson
authors.forename: Armelle
authors.initials: A
authors.lastname: Arnoux
authors.forename: Michel
authors.initials: M
authors.lastname: Marty
authors.forename: Laurent
authors.initials: L
authors.lastname: Hannoun
authors.forename: Didier
authors.initials: D
authors.lastname: Samuel
authors.forename: Patrice
authors.initials: P
authors.lastname: Debré
authors.forename: Vincent
authors.initials: V
authors.lastname: Vieillard
mesh_terms: D000328:Adult; D000368:Aged; D000954:Antigens, Surface / Q000378:metabolism; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D016207:Cytokines / Q000378:metabolism; D003587:Cytomegalovirus / Q000235:genetics / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000378:metabolism*; D009369:Neoplasms / Q000209:etiology*; D010641:Phenotype; D012307:Risk Factors; D055815:Young Adult
chemical_list: D000954:Antigens, Surface; D016207:Cytokines; C527059:KLRC2 protein, human; D055654:NK Cell Lectin-Like Receptor Subfamily C