Heterogeneous effects of B7-1 and B7-2 in the induction of both protective and therapeutic anti-tumor immunity against different mouse tumors.
Experimental mouse tumors are classified as intrinsically immunogenic when, after a single injection into syngeneic mice as nonreplicating cell vaccines, they elicit a protective immune response against a subsequent lethal challenge. Tumors that do not retain this residual immunogenicity are defined as poorly immunogenic or nonimmunogenic. The expression of the B7-1 co-stimulatory molecule on immunogenic tumors can further increase their capacity to induce a T cell-dependent anti-tumor immunity, whereas it has limited effects on nonimmunogenic tumors. Recently, B7-2, a second molecule with an apparently similar co-stimulatory activity, has been cloned. In this report, we compare the efficiency of nonreplicating cells from one immunogenic and two nonimmunogenic mouse tumors transfected with B7-1 or B7-2 in the induction of protective and curative anti-tumor immunity. Immunogenic lymphoma cells expressing B7-1 or B7-2 are equally effective in both protecting against a subsequent challenge and curing established tumors. By contrast, nonimmunogenic adenocarcinoma and melanoma cells expressing B7-2 provide superior protective immunity, and only B7-2+ adenocarcinoma cells induce an efficient curative immunity. CD8+ and polymorphonuclear cells, but not CD4+ T cells, are critically involved in the rejection of the adenocarcinoma elicited by both B7-1+ and B7-2+ vaccines. These data indicate that B7-1 and B7-2 are not redundant co-stimulatory molecules and that, in these experimental models, B7-2 is superior to B7-1 in the induction of an efficient immunity when the immunogenicity of a tumor is a limiting factor.
Martin-Fontecha
A
A
Unità d'Immunochimica, DIBIT, Istituto Scientifico San Raffaele, Milano, Italy.
Cavallo
F
F
Bellone
M
M
Heltai
S
S
Iezzi
G
G
Tornaghi
P
P
Nabavi
N
N
Forni
G
G
Dellabona
P
P
Casorati
G
G
D000230:Adenocarcinoma / Q000276:immunology; D000818:Animals; D015703:Antigens, CD / Q000494:pharmacology* / Q000627:therapeutic use*; D018122:B7-1 Antigen / Q000494:pharmacology* / Q000627:therapeutic use*; D051940:B7-2 Antigen; D001483:Base Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive; D008213:Lymphocyte Activation; D008223:Lymphoma / Q000276:immunology; D008546:Melanoma, Experimental / Q000276:immunology; D008562:Membrane Glycoproteins / Q000494:pharmacology* / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009374:Neoplasms, Experimental / Q000276:immunology / Q000517:prevention & control* / Q000628:therapy*; D015398:Signal Transduction / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection / Q000276:immunology; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; C497965:Cd86 protein, mouse; D008562:Membrane Glycoproteins