title: Total loss of HLA class I expression on a melanoma cell line after growth in nude mice in absence of autologous antitumor immune response.
abstract: Loss of HLA class I expression on tumor cells is a frequent event as an immune escape mechanism. Seven different altered HLA phenotypes have been defined in tumors. Various molecular mechanisms have been described as responsible for HLA class I loss. HLA class I expression alterations occur successively and unpredictably during tumor progression in vivo and immunoselection has been implicated in this process. We present an experimental xenograft model in which melanoma cell line Ando-2 injected into athymic nude mice lost total surface HLA class I expression and exhibited HLA class II cell surface expression. A strong down-regulation of HLA class I expression and de novo HLA class II expression were also found when Ando-2 melanoma cells were injected into SCID-Beige mice. These phenomena were reproducible and were only observed in local growth in nude or SCID-Beige mice and not in vitro after multiple passages. HLA class I surface expression was recovered after IFN-gamma treatment, indicating regulatory defects. The mechanism implicated in loss of HLA class I molecule expression were a down-regulation of different components of antigen processing machinery and HLA class I heavy chains. These data suggest that HLA class I alterations can also occur in absence of autologous adaptive immune response. This is a good experimental in vivo model to study the relationship between tumor progression and HLA class I alterations.
authors.affiliation: Servicio de Análisis Clínicos, Hospital Universitario Virgen de las Nieves, Universidad de Granada, Granada, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Paco
authors.affiliation: Servicio de Análisis Clínicos, Hospital Universitario Virgen de las Nieves, Universidad de Granada, Granada, Spain.
authors.forename: Angel Miguel
authors.initials: AM
authors.lastname: Garcia-Lora
authors.affiliation: Servicio de Análisis Clínicos, Hospital Universitario Virgen de las Nieves, Universidad de Granada, Granada, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Casares
authors.affiliation: Servicio de Análisis Clínicos, Hospital Universitario Virgen de las Nieves, Universidad de Granada, Granada, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Cabrera
authors.affiliation: Departamento Ciencias de La Salud, Universidad de Jaén, Jaén, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Algarra
authors.affiliation: Servicio de Análisis Clínicos, Hospital Universitario Virgen de las Nieves, Universidad de Granada, Granada, Spain.
authors.forename: Antonia
authors.initials: A
authors.lastname: Collado
authors.affiliation: Servicio de Análisis Clínicos, Hospital Universitario Virgen de las Nieves, Universidad de Granada, Granada, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Maleno
authors.affiliation: Servicio de Análisis Clínicos, Hospital Universitario Virgen de las Nieves, Universidad de Granada, Granada, Spain.
authors.forename: Federico
authors.initials: F
authors.lastname: Garrido
authors.affiliation: Servicio de Análisis Clínicos, Hospital Universitario Virgen de las Nieves, Universidad de Granada, Granada, Spain.
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Lopez-Nevot
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D018450:Disease Progression; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D016678:Genome / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008545:Melanoma / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D012333:RNA, Messenger