Total loss of HLA class I expression on a melanoma cell line after growth in nude mice in absence of autologous antitumor immune response.
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.
Paco
Laura
L
Servicio de Análisis Clínicos, Hospital Universitario Virgen de las Nieves, Universidad de Granada, Granada, Spain.
Garcia-Lora
Angel Miguel
AM
Servicio de Análisis Clínicos, Hospital Universitario Virgen de las Nieves, Universidad de Granada, Granada, Spain.
Casares
Carlos
C
Servicio de Análisis Clínicos, Hospital Universitario Virgen de las Nieves, Universidad de Granada, Granada, Spain.
Cabrera
Carmen
C
Servicio de Análisis Clínicos, Hospital Universitario Virgen de las Nieves, Universidad de Granada, Granada, Spain.
Algarra
Ignacio
I
Departamento Ciencias de La Salud, Universidad de Jaén, Jaén, Spain.
Collado
Antonia
A
Servicio de Análisis Clínicos, Hospital Universitario Virgen de las Nieves, Universidad de Granada, Granada, Spain.
Maleno
Isabel
I
Servicio de Análisis Clínicos, Hospital Universitario Virgen de las Nieves, Universidad de Granada, Granada, Spain.
Garrido
Federico
F
Servicio de Análisis Clínicos, Hospital Universitario Virgen de las Nieves, Universidad de Granada, Granada, Spain.
Lopez-Nevot
Miguel Angel
MA
Servicio de Análisis Clínicos, Hospital Universitario Virgen de las Nieves, Universidad de Granada, Granada, Spain.
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
D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D012333:RNA, Messenger