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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 Immunity¹

Alfonso Martín-Fontecha^2,*, Monica Moro^*, Maria Cristina Crosti^*, Fabrizio Veglia, Giulia Casorati^3,* and Paolo Dellabona^3,*

^* Unità d’Immunochimica, DIBIT, Cancer Immunotherapy and Gene Therapy Program; and Unità di Biostatistica, Istituto Scientifico H. San Raffaele, Milan, Italy

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- 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- 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.

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