Utilizing the 2017–2018 seasonal influenza vaccine as a treatment for cancer

Abstract

Abstract In recent years, immunotherapy has yielded increased survival for cancer patients; however, a significant percentage of patient tumors remain refractory to immunotherapy. This is due in part to the absence of an inflamed tumor microenvironment. In our effort to utilize anti-pathogen vaccination to recruit immune cells to un-infiltrated (cold) tumors, we observed that intratumoral injection of influenza A/PR8/H1N1 lysate (but not live virus) reduced B16-F10 melanoma growth (p<0.01). Towards determining whether FDA-approved human vaccines could likewise be utilized, we administered a quadrivalent 2017–2018 human seasonal influenza vaccine via intratumoral injection to mice, significantly slowing tumor growth relative to that of PBS-injected controls (p<0.05). Analysis of RNA from tumor homogenates via the NanoString PanCancer Immune Profiling Panel indicated upregulation of transcripts for chemokines (CCL5, CXCL9), immune checkpoints (PD-L1, LAG3), and HLA molecules – hallmarks of an inflamed (hot) tumor phenotype. In addition to halting tumor growth, intratumoral administration of the human influenza vaccine protected mice from subsequent intranasal influenza challenge. Our findings suggest that intratumoral administration of human vaccines can reduce tumor growth, in part by converting “cold” tumors into “hot” (immune-infiltrated) tumors, while simultaneously providing protection against infection. Future studies will address the efficacy of vaccination in humanized mouse models and the possibility of synergy with checkpoint blockade therapies, in an effort to evaluate the potential of microbial-based therapies as a dual vehicle for cancer treatment and infection prevention.