Loss of B7-H1 enhances the tumor rejection capabilities of murine anti-tumor CD8+ T cells

Attempts to create effective immunotherapies against metastatic solid tumors have long been hindered by the ability of the tumor to evade the immune response of the host. One possible mechanism for mediating the full therapeatuic potential of anti-tumor immunotherapies is to block inhibitory molecules that may dampen the anti-tumor immune response, such as PD-1 and its ligand B7-H1. The PD-1/B7-H1 signaling pathway is believed to play a critical role in negatively regulating T cell responses by inducing anergy and functional inactivation. In our model of murine malignant mesothelioma (MM), CD8+ T cells are a critical component of tumor immunity against tumors generated by the AB1-HA cell line. We demonstrate that B7-H1 deficiency elicits slower tumor progression due to a more responsive CD44hi CD8+ T cell repertoire while altering the tumor microenvironment to become more permissive to infiltrating lymphocytes. Ultimately, tumor eradication is achieved by increasing the precursor frequencies of tumor-specific CD8+ T cells without recurrence of tumor. Therefore, our findings support the notion that PD-1/B7-H1 plays an inhibitory role against anti-tumor response and that blocking this signaling pathway, in conjunction with immunotherapy, will induce effective tumor rejection against non-immunogenic solid tumors.