ORIGINAL ARTICLE

Cancer Immunology, Immunotherapy

, Volume 49, Issue 11, pp 621-628

Multiple mechanisms of immune evasion can coexist in melanoma tumor cell lines derived from the same patient

  • L. M. RealAffiliated withServicio de Análisis Clínicos e Inmunología, Hospital Universitario Virgen de las Nieves, Universidad de Granada, Avda. Constitución s/n, 18014 Granada, Spain e-mail: fruizc@goliat.ugr.es Tel.: +34-958-278381; Fax: +34-958-241233
  • , P. JimenezAffiliated withServicio de Análisis Clínicos e Inmunología, Hospital Universitario Virgen de las Nieves, Universidad de Granada, Avda. Constitución s/n, 18014 Granada, Spain e-mail: fruizc@goliat.ugr.es Tel.: +34-958-278381; Fax: +34-958-241233
  • , A. KirkinAffiliated withDepartment of Tumor Cell Biology, Division of Cancer Biology, Danish Cancer Society, Copenhagen, Denmark
  • , A. SerranoAffiliated withServicio de Análisis Clínicos e Inmunología, Hospital Universitario Virgen de las Nieves, Universidad de Granada, Avda. Constitución s/n, 18014 Granada, Spain e-mail: fruizc@goliat.ugr.es Tel.: +34-958-278381; Fax: +34-958-241233
  • , A. GarcíaAffiliated withServicio de Análisis Clínicos e Inmunología, Hospital Universitario Virgen de las Nieves, Universidad de Granada, Avda. Constitución s/n, 18014 Granada, Spain e-mail: fruizc@goliat.ugr.es Tel.: +34-958-278381; Fax: +34-958-241233
  • , J. CantónAffiliated withServicio de Análisis Clínicos e Inmunología, Hospital Universitario Virgen de las Nieves, Universidad de Granada, Avda. Constitución s/n, 18014 Granada, Spain e-mail: fruizc@goliat.ugr.es Tel.: +34-958-278381; Fax: +34-958-241233
  • , J. ZeuthenAffiliated withDepartment of Tumor Cell Biology, Division of Cancer Biology, Danish Cancer Society, Copenhagen, Denmark
  • , F. GarridoAffiliated withServicio de Análisis Clínicos e Inmunología, Hospital Universitario Virgen de las Nieves, Universidad de Granada, Avda. Constitución s/n, 18014 Granada, Spain e-mail: fruizc@goliat.ugr.es Tel.: +34-958-278381; Fax: +34-958-241233
  • , F. Ruiz-CabelloAffiliated withServicio de Análisis Clínicos e Inmunología, Hospital Universitario Virgen de las Nieves, Universidad de Granada, Avda. Constitución s/n, 18014 Granada, Spain e-mail: fruizc@goliat.ugr.es Tel.: +34-958-278381; Fax: +34-958-241233

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Abstract

 Progressive tumor growth may be associated with suppression of the immune response. Many different mechanisms may contribute to immune evasion. We investigated some of these mechanisms in melanoma cells lines generated from two patients. These cell lines show a complex pattern of altered HLA expression; however, the resulting phenotype did not satisfactorily explain the simultaneous evasion of T and NK cell cytotoxicity. Two additional alterations have now been detected in these melanoma cell lines: (1) resistance to FAS-induced apoptosis caused by defective FAS gene expression, and (2) constitutive expression of immunosuppressive cytokines. Our results show that several of the major mechanisms for immune evasion may coexist in a single tumor. This suggests that tumor progression may give rise to an extremely resistant phenotype, which may be an impediment to some immunotherapeutic strategies. We hypothesize that the simultaneous presence of several mechanisms involved in tumor immune evasion must be the result of progressive selection of characteristics that are advantageous for tumor survival in a competent host. Our findings do not support the possibility that FASL expression is a common mechanism of evasion of immune response in melanoma cells.

Key words Melanoma Metastases Selection FASL Immune evasion