Cancer Immunology, Immunotherapy

, Volume 58, Issue 9, pp 1517–1526 | Cite as

Expression of adhesion molecules and ligands for activating and costimulatory receptors involved in cell-mediated cytotoxicity in a large panel of human melanoma cell lines

  • Javier G. Casado
  • Graham Pawelec
  • Sara Morgado
  • Beatriz Sanchez-Correa
  • Elena Delgado
  • Inmaculada Gayoso
  • Esther Duran
  • Rafael Solana
  • Raquel Tarazona
Focussed Research Review


Knowledge of the interactions between MHC-unrestricted cytotoxic effector cells and solid tumour cells is essential for introducing more effective NK cell-based immunotherapy protocols into clinical practise. Here, to begin to obtain an overview of the possible universe of molecules that could be involved in the interactions between immune effector cells and melanoma, we analyse the surface expression of adhesion and costimulatory molecules and of ligands for NK-activating receptors on a large panel of cell lines from the “European Searchable Tumour Cell Line and Data Bank” (ESTDAB, and discuss their potential role in the immune response against this tumour. We show that most melanoma cell lines express not only adhesion molecules that are likely to favour their interaction with cells of the immune system, but also their interaction with endothelial cells potentially increasing their invasiveness and metastatic capacity. A high percentage of melanoma cell lines also express ligands for the NK-activating receptor NKG2D; whereas, the majority express MICA/B molecules, ULBP expression, however, was rarely found. In addition to these molecules, we also found that CD155 (poliovirus receptor, PVR) is expressed by the majority of melanoma cell lines, whereas CD112 (Nectin-2) expression was rare. These molecules are DNAM-1 ligands, a costimulatory molecule involved in NK cell-mediated cytotoxicity and cytokine production that also mediates costimulatory signals for triggering naïve T cell differentiation. The phenotypical characterisation of adhesion molecules and ligands for receptors involved in cell cytotoxicity on a large series of melanoma cell lines will contribute to the identification of markers useful for the development of new immunotherapy strategies.


Melanoma ESTDAB NK cells Cell-mediated cytotoxicity MICA/B Adhesion Activating receptor Cancer Tumour 



Work in the laboratories of R.T., R.S. and G.P. was partially supported by grants SAF2003/05184 and SAF2006/03687 (to R.T.) from the Spanish Ministry of Education and Science, FIS PI061320 (to R.S.) from the Spanish Ministry of Health, 03/2 and 3PR05A012, GRU07044 and GRU08077 (to R.T.) from Junta de Extremadura, cofinanced by the European Regional Development Fund (FEDER) and DFG-SFB685-B4 (to G.P.). The establishment of the database and cell bank was supported by the European Commission (contract QLRICT-2001-01325) (see This work was also supported by contracts QLRT-2001-00668 (Outcome and Impact of Specific Treatment in European Research on Melanoma, OISTER), QLK6-CT2002-02283 (T cells in Ageing, T-CIA) from the 5th Framework Program of the European Union and 503306 from the 6th FP (European Network for the identification and validation of antigens and biomarkers in cancer and their application in clinical tumor immunology, ENACT). J.G.C. received a post-doctoral fellowship associated to the 5th Framework Programme, contract QLRT-2001-00668 (OISTER) and B.S.C and S.M. are pre-doctoral fellows from Junta de Extremadura. Special thanks are due to M.R. Gonzalez and J.J. Gordillo for their technical assistance in cell culture and flow cytometry.


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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Javier G. Casado
    • 1
  • Graham Pawelec
    • 2
  • Sara Morgado
    • 1
  • Beatriz Sanchez-Correa
    • 1
  • Elena Delgado
    • 1
  • Inmaculada Gayoso
    • 4
  • Esther Duran
    • 3
  • Rafael Solana
    • 4
  • Raquel Tarazona
    • 1
  1. 1.Immunology Unit, Department of PhysiologyUniversity of ExtremaduraCáceresSpain
  2. 2.Center for Medical ResearchUniversity of TübingenTübingenGermany
  3. 3.Department of Comparative PathologyUniversity of ExtremaduraCáceresSpain
  4. 4.Immunology Unit, Department of Cellular Biology, Physiology and Immunology, Faculty of MedicineUniversity of CórdobaCordobaSpain

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