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Natural Killer Receptors on CD8 T Cells and Natural Killer Cells from Different HLA-C Phenotypes in Melanoma Patients

Authors' Affiliations: ¹ Immunology Service and ² Dermatology Section, Virgen de la Arrixaca University Hospital; and ³ Department of Bio-Statistics, School of Medicine, University of Murcia, Murcia, Spain

Requests for reprints: Maria Rocío Álvarez-López, Immunology Service, Virgen de la Arrixaca University Hospital, Ctra. Madrid-Cartagena, 30120 El Palmar, Murcia, Spain. Phone: 34-968-36-90-50; Fax: 34-968-36-96-78; E-mail: mdrocio.alvarez{at}carm.es.

Purpose: Because immune mechanisms involved in cutaneous melanoma have not been fully elucidated, efforts have been made to achieve prognosis markers and potential targets for immune therapies, but they have not been entirely fruitful thus far. Therefore, the goal of this study was to investigate the involvement of early changes in CD8 T cells and CD56 natural killer (NK) cells expressing NK receptors in different HLA-C dimorphism groups of melanoma patients.

Experimental Design: CD8 T cells and CD56 NK cells were analyzed in 41 patients and 39 sex- and age-matched controls with different HLA-C genotypes by flow cytometry. HLA-C dimorphism at position 80 was tested by PCR sequence-specific primers and PCR sequence-specific oligonucleotide to examine whether it could mediate in the emergence of cells expressing killer cell immunoglobulin-like receptors.

Results: Thirty-five of 41 patients had benign sentinel node, and showed an imbalance in the absolute number of CD8⁺DR⁺ or CD8⁺CD161⁺ peripheral blood T cells according to the CD28 coexpression compared with controls. CD8⁺CD28^–CD158a⁺ T and CD56⁺CD158a⁺ NK cells were significantly increased in HLA-C^Lys80 homozygous nonmetastatic patients, whereas only CD56⁺CD158a⁺ NK cells increased in heterozygous ones. An up-regulation of the CD158a KIR receptor was also seen on NK cells but not in T cells of patients at advanced disease stages.

Conclusions: This work provides, for the first time, evidence of immune activation in early stages of cutaneous melanoma, together with an increase of cells expressing CD158a in patients bearing the corresponding HLA-C ligand, which may be important to evaluate the disease progression and to use individualized immune therapeutic approaches.