Vaccination with mouse mammary adenocarcinoma cells coexpressing B7-1 (CD80) and B7-2 (CD86) discloses the dominant effect of B7-1 in the induction of antitumor immunity.
Nonreplicating TS/A mammary adenocarcinoma cells expressing B7-2 (CD86) (TS/A-2) are more immunogenic than those expressing B7-1 (CD80) (TS/A-1), indicating that B7-1 and B7-2 display nonredundant costimulatory effects in inducing antitumor responses. Whereas transfection of B7-2 cDNA into TS/A-1 cells does not improve their immunogenicity, transfection of B7-1 cDNA into TS/A-2 cells (TS/A-2/1) decreases their immunogenicity in a manner that is directly related to the surface levels of B7-1. Ab blocking of B7-1 on TS/A-2/1 cells before their injection in vivo restores the higher immunogenicity characteristic of single B7-2 transfectants, indicating therefore that B7-1 actively modulates the B7-2-dependent costimulation. The expression of B7-1 also modifies quantitatively the balance of endogenous IFN-gamma and IL-4 induced in vivo by TS/A-2 vaccines. In fact, we find that vaccination with TS/A-2/1 cells results in the production of more IFN-gamma and less IL-4 than TS/A-2 vaccines, a pattern comparable to that induced by TS/A-1 cells. Thus, in the TS/A model of antitumor response, B7-1 modulates B7-2-dependent costimulatory effects in a dominant, noncompetitive way.
Martín-Fontecha
A
A
Unità d'Immunochimica, DIBIT, Cancer Immunotherapy and Gene Therapy Program; and Unità di Biostatistica, Istituto Scientifico H. San Raffaele, Milan, Italy.
Moro
M
M
Crosti
M C
MC
Veglia
F
F
Casorati
G
G
Dellabona
P
P
D000230:Adenocarcinoma / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000096:biosynthesis*; D018122:B7-1 Antigen / Q000096:biosynthesis* / Q000276:immunology; D051940:B7-2 Antigen; D019496:Cancer Vaccines / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D015674:Mammary Neoplasms, Animal / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D014407:Tumor Cells, Cultured
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019496:Cancer Vaccines; C497965:Cd86 protein, mouse; D008562:Membrane Glycoproteins; D015847:Interleukin-4; D007371:Interferon-gamma