Combination immunotherapy utilizing influenza infection and PD-1 blockade reduces lung melanoma tumor growth (TUM2P.1011)

Abstract

Emerging epidemiological studies report increased cancer occurrence in patients with chronic viral infections, even when such infections are non-oncogenic and not in the same tissue as the cancer. In our recent studies, we observed decreased anti-tumor immune responses in the context of concomitant infection. Specifically, we discovered that anti-melanoma (gp100) CD8+ T cell responses in mice challenged with melanoma are shunted from the tumor site (skin) to the site of influenza infection (lung), leading to faster tumor growth and hastened host death. We observed similar findings with multiple tumor and virus combinations, including patient-derived melanomas in humanized mice infected with HIV. Based on this infection-mediated shunting of anti-tumor CD8+ T cells to the infection site, and towards developing related therapeutic interventions, we sought to determine whether an infection in a particular tissue would improve anti-tumor responses against a tumor also in that same tissue. We discovered that influenza infection within the lungs resulted in 51% fewer tumor foci within the lungs compared to no infection. Tumor foci were further reduced with systemic PD-1 blockade (more than 70% fewer tumor foci compared to no infection or PD-1 blockade alone). Future studies will further dissect the mechanisms underlying these findings in the setting of viral infection. We ultimately aim to translate these findings to combination cancer immunotherapies utilizing viral infections.