Heterogeneous effects of B7‐1 and B7‐2 in the induction of both protective and therapeutic anti‐tumor immunity against different mouse tumors

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Abstract
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.