Immunization with MHC class I-negative but not -positive HPV16-associated tumour cells inhibits growth of MHC class I-negative tumours.
Loss or downregulation of MHC class I molecules on tumour cells is a common mechanism by which tumours can escape from T-cell mediated immune responses. In this study we have investigated the immunologic crossreactivity between murine tumour cell lines expressing human papilloma virus (HPV) 16-derived E6/E7 oncoproteins with distinct surface expression of MHC class I molecules. The aims of this study were to demonstrate whether immune responses capable of coping with MHC class I-positive tumours can also be effective against their MHC class I-deficient derivatives and whether it is possible to induce immunity against MHC class I-deficient tumours by cellular vaccines based on MHC class I-deficient tumour cell lines. Our data showed that immunization with MHC class I-deficient but not with MHC class I positive tumour cells inhibited the growth of MHC class I-deficient tumours. In vivo depletion studies revealed that the mechanisms underlying effective immune responses against MHC class I-negative tumours in animals immunized with MHC class I-deficient tumour cells involved natural killer cells. The presented findings are of particular clinical relevance in the sense of construction of vaccines directed against a broad spectrum of HPV-associated tumours.
Reinis
Milan
M
Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
Símová
Jana
J
Indrová
Marie
M
Bieblová
Jana
J
Pribylová
Hana
H
Moravcová
Simona
S
Jandlová
Tána
T
Bubeník
Jan
J
D000818:Animals; D019496:Cancer Vaccines / Q000627:therapeutic use; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003429:Cross Reactions; D015395:Histocompatibility Antigens Class I / Q000032:analysis / Q000276:immunology*; D052162:Human papillomavirus 16 / Q000276:immunology*; D007114:Immunization; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000276:immunology / Q000628:therapy* / Q000821:virology*
D019496:Cancer Vaccines; D015395:Histocompatibility Antigens Class I