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CD8 T cells expressing NK associated receptors are increased in melanoma patients and display an effector phenotype

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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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Authors and Affiliations

  1. Department of Cellular Biology, Physiology and Immunology Faculty of Medicine, University of Córdoba, Córdoba, Spain

    Javier G. Casado, Olga DelaRosa, Esther Peralbo, José Peña & Rafael Solana

  2. Department of Plastic Surgery, Reina Sofia University Hospital, Córdoba, Spain

    Rocío Soto & Luis Rioja

  3. Research Unit, Reina Sofia University Hospital, Córdoba, Spain

    Maria del Carmen Muñoz-Villanueva

  4. Veterinary Faculty, Department of Physiology, Immunology Unit, University of Extremadura, Cáceres, Spain

    Raquel Tarazona

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  1. Javier G. Casado
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  2. Rocío Soto
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  3. Olga DelaRosa
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  4. Esther Peralbo
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  5. Maria del Carmen Muñoz-Villanueva
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  6. Luis Rioja
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  7. José Peña
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  8. Rafael Solana
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  9. Raquel Tarazona
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Correspondence to Raquel Tarazona.

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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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