Co‐expression of B7‐1 and ICAM‐1 on tumors is required for rejection and the establishment of a memory response

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Abstract
Although the transfection of B7‐1 cDNA into a few mouse tumor cell lines can induce anti‐tumor T cell immunity, its expression alone is ineffective in many other tumor cell lines tested. We were interested to study what factors limit B7‐1 co‐stimulatory activity, and decided to investigate whether B7‐1 requires the cooperation of ICAM‐1 to provide the minimal co‐stimulatory signal for establishing an efficient anti‐tumor immunity. We show that the transfection of B7‐1 cDNA into three ICAM‐1+ (plasmocytoma J558L, T lymphomas EL‐4 and RMA), but not into two ICAM‐1− tumor cell lines (adenocarcinoma TS/A and melanoma B16.F1), is sufficient to induce their complete rejection in syngeneic mice. The expression of ICAM‐1 is necessary for the rejection of the B7 expressing tumors, since the primary response elicited by B7‐1+ EL‐4 and RMA clones expressing reduced levels of ICAM‐1 is severely reduced. Furthermore, super‐transfection of ICAM‐1 cDNA into B7‐1+ adenocarcinoma and melanoma clones optimizes their primary rejection. Histologic examination of transfected tumors reveals that B7‐1 and ICAM‐1 exert a potent pro‐inflammatory activity. The intra‐tumor infiltration is composed of both eosinophils and lymphomono‐cytes, and is already massive 5 days after the tumor challenge. The primary rejection of the B7‐1+ ICAM‐1+ tumors depends critically on CD8+ T cells, natural killer cells and granulocytes, but is independent of CD4+ T cells. Remarkably, in addition to its effects on the early phases of the immune response, the co‐expression of ICAM‐1 and B7‐1 on tumors is also necessary for the efficient induction of a memory response. In fact, only the primary challenge with B7‐1+, ICAM‐1+ tumor cells protects the majority of the mice from a second injection of parental tumor cells. Collectively, our findings indicate that B7‐1 and ICAM‐1 are fundamental components for triggering the primary rejection of tumors and establishing a protective memory response. These findings may help to define new strategies for the rational application of co‐stimulation in tumor immunotherapy.