IRF-1 suppresses tumor formation and protects against tumor rechallenge in a murine model of breast carcinoma: The role of tumor specific immunity

Abstract

Introduction. IRF-1 is involved in multiple stages of the immune response. We previously demonstrated that IRF-1 causes apoptosis in breast cancer; however, the role of immune up regulation by IRF-1 remains to be elucidated. We hypothesize that IRF-1 expression results in enhanced tumor immunogenicity of murine breast cancer in vivo. Methods. Murine breast carcinoma C3L5 cells were mock, Ad-Psi5 (empty vector), or Ad-IRF-1 (recombinant adenovirus expressing IRF-1) infected and then injected s.c. into syngeneic C3H/HeJ and nude mice at 500,000 cells/mouse. In subsequent experiment, mock, Ad-Psi5 or Ad-IRF-1-infected cells were injected into C3H/HeJ mice, and at 3 weeks, tumor, if present, was excised, and mice were rechallenged with 500,000 uninfected, parental tumor cells into contralateral flank. Results. Ex vivo transduction of C3L5 cells with Ad-IRF-1 prevented tumor formation in 80% of syngeneic mice, whereas 0% of nude mice were protected. Mock and Ad-Psi5 animals all developed tumor. “Vaccination” with Ad-IRF-1-treated cells protected 60% syngeneic mice from tumor formation after rechallenge with parental tumor cells. Vaccination with mock and Ad-Psi5-treated cells did not provide any protection. Median tumor-free survival was 70 days for Ad-IRF-1 (the length of the experiment), 27 days for Ad-Psi5, and 29 days for mock ( P < 0.05 by log rank test). Conclusions. Tumor suppression by Ad-IRF-1 is immune-mediated to a significant extent, involving T cells. An adaptive immune response to parental tumor cell rechallenge was achieved, reflecting tumor specific immunity. These data support the use of agents that increase IRF-1 in breast cancer.