Identification of different tumor escape mechanisms in several metastases from a melanoma patient undergoing immunotherapy.
The cytotoxic activity of T cells selects the outgrowth of tumor cells that escape from immune surveillance by different strategies. The different mechanisms that interfere with immune recognition and limit vaccination efficiency are still poorly understood. We analysed six cell lines established from different metastases of melanoma patient UKRV-Mel-20 for specific characteristics known to have an impact on the tumor-T cell interaction: (1) alterations in the HLA class I phenotype, (2) expression of Fas/CD95, and (3) expression of specific cytokines and chemokines. One of the cell lines, UKRV-Mel-20f, exhibited an HLA class I haplotype loss and just this cell line was also characterised by the expression of Fas/CD95 and of relatively high levels of proinflammatory chemokines suggesting that the cytotoxic activity of tumor-infiltrating T cells might have selected the outgrowth of this tumor cell variant. All other cell lines analysed showed no alterations in HLA class I expression, but, in contrast to UKRV-Mel-20f, expressed much lower levels of Fas/CD95 and of proinflammatory chemokines and some of them produced high levels of immunosuppressive TGF-beta1. These results suggest that in patient UKRV-Mel-20, tumor cells interfere with T cell recognition by different strategies which might partially explain why this patient did not have a clinical response to an autologous tumor cell vaccine.
Méndez
Rosa
R
Servicio de Análisis Clínicos e Inmunología, Hospital Universitario Virgen de las Nueves, Avda Fuerzas Armadas s/n, 18014, Granada, Spain.
Ruiz-Cabello
Francisco
F
Rodríguez
Teresa
T
Del Campo
Ana
A
Paschen
Annette
A
Schadendorf
Dirk
D
Garrido
Federico
F
D001932:Brain Neoplasms / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D019496:Cancer Vaccines / Q000627:therapeutic use; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D053222:Fas Ligand Protein / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D007167:Immunotherapy; D019656:Loss of Heterozygosity; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008545:Melanoma / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D018895:Microsatellite Repeats / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000276:immunology* / Q000556:secondary / Q000628:therapy; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014407:Tumor Cells, Cultured; D019139:Tumor Escape / Q000276:immunology*
D019496:Cancer Vaccines; D018925:Chemokines; D016207:Cytokines; D053222:Fas Ligand Protein; D015395:Histocompatibility Antigens Class I; D053773:Transforming Growth Factor beta1