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Expansion of CMV-mediated NKG2C+ NK cells associates with the development of specific de novo malignancies in liver-transplanted patients
- Source :
- Journal of immunology (Baltimore, Md. : 1950). 192(1)
- Publication Year :
- 2013
-
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.
- Subjects :
- Adult
Male
medicine.medical_treatment
T cell
Immunology
Cytomegalovirus
Biology
Immunophenotyping
Young Adult
Antigen
Risk Factors
Cell Line, Tumor
Neoplasms
medicine
Immunology and Allergy
Cluster Analysis
Humans
Aged
Innate immune system
Immunosuppression
Middle Aged
Liver Transplantation
Transplantation
Killer Cells, Natural
Cytokine
medicine.anatomical_structure
Phenotype
Antigens, Surface
Cytomegalovirus Infections
Cytokines
Female
NK Cell Lectin-Like Receptor Subfamily C
Subjects
Details
- ISSN :
- 15506606
- Volume :
- 192
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Accession number :
- edsair.doi.dedup.....2171439377e4ac10505c6acad675ea14