Abstract
CD8+ T cells can express NK-associated receptors (NKRs) that may regulate their cytolytic function. We have characterized the expression of several NKRs on peripheral blood CD8+ T cells from melanoma patients and compared them to age-matched healthy donors. The analysis performed includes HLA class I specific receptors (KIRs, LILRB1 and CD94/NKG2) and other NK receptors like CD57, CD56 and CD16. Melanoma patients showed a higher variability in the expression of NKRs on circulating CD8+ T cells than age-matched healthy donors. NKR expression on CD8+ T cells from melanoma patients showed a significant increase of KIR2DL2/L3/S2 (mAb gl183), CD244, CD57, CD56 and CD16. We have also found an increase of CD8+ CD28− CD27− T cells in melanoma patients. This subset represents terminally differentiated effector cells expressing CD244 and high levels of perforin. The expression of NKRs was also mainly restricted to this T cell subset. Altogether, circulating CD8+ T cells from melanoma patients display a distinct phenotype characterized by downregulation of costimulatory molecules and higher expression of NKRs. We suggest that the increased expression of NKRs on T cells may contribute to the final outcome of the immune response against melanoma both stimulating or inhibiting activation and differentiation to effector cells. Blocking inhibitory receptor function and enhancing activating receptors may represent new strategies with therapeutic potential against melanoma.
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Abbreviations
- CTL:
-
Cytotoxic T Lymphocyte
- Ig:
-
Immunoglobulin
- ILT:
-
Immunoglobulin like transcripts
- ITIM:
-
Immunoreceptor tyrosine-based inhibition motif
- ITAM:
-
Immunoreceptor tyrosine-based activation motif
- KIR:
-
Killer cell Immunoglobulin-like receptors
- LILR:
-
Leukocyte immunoglobulin-like receptors
- NK cell:
-
Natural killer cell
- NKR:
-
Natural killer cell-associated receptor
- TCR:
-
T cell receptor
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Acknowledgements
This work was supported by grants QLRT-2001-00668 (Outcome and Impact of Specific Treatment in European Research on Melanoma, OISTER) and QLK6-CT2002-02283 (T cells in Ageing, T-CIA) from the 5th Framework Program of the European Union, FIS01/0478, FIS03/1383 (to R.S.), FIS00/0853 (to R.T.) from the Ministry of Health, SAF2003-05184 (to R.T.) from the Ministry of Science and Technology and 03/2 (to R.T.) from the “Consejería de Sanidad y Consumo” Junta de Extremadura, (Spain).
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Casado, J.G., Soto, R., DelaRosa, O. et al. CD8 T cells expressing NK associated receptors are increased in melanoma patients and display an effector phenotype. Cancer Immunol Immunother 54, 1162–1171 (2005). https://doi.org/10.1007/s00262-005-0682-5
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DOI: https://doi.org/10.1007/s00262-005-0682-5