Rosato et al. showed that injecting an adjuvant-free viral peptide intratumorally in mice rapidly reactivated existing antiviral memory CD8+ T cells (found in the blood and in the tumor), promoted activation and accumulation of CD8+ T cells, NK cells, and DCs within tumors, delayed tumor growth, and synergized with anti-PD-L1 to eliminate anti-PD-L1-resistant tumors. Most cured mice were protected when rechallenged in the opposite flank, indicating development of systemic memory. Human endometrial or colon tumor slice cultures treated with an adjuvant-free viral peptide ex vivo exhibited immune activation as shown by RNAseq.
The immunosuppressive tumor microenvironment limits the success of current immunotherapies. The host retains memory T cells specific for previous infections throughout the entire body that are capable of executing potent and immediate immunostimulatory functions. Here we show that virus-specific memory T cells extend their surveillance to mouse and human tumors. Reactivating these antiviral T cells can arrest growth of checkpoint blockade-resistant and poorly immunogenic tumors in mice after injecting adjuvant-free non-replicating viral peptides into tumors. Peptide mimics a viral reinfection event to memory CD8+ T cells, triggering antigen presentation and cytotoxic pathways within the tumor, activating dendritic cells and natural killer cells, and recruiting the adaptive immune system. Viral peptide treatment of ex vivo human tumors recapitulates immune activation gene expression profiles observed in mice. Lastly, peptide therapy renders resistant mouse tumors susceptible to PD-L1 blockade. Thus, re-stimulating known antiviral immunity may provide a unique therapeutic approach for cancer immunotherapy.
Author Info: (1) Department of Microbiology and Immunology, Center for Immunology, University of Minnesota, Minneapolis, MN, 55455, USA. (2) Department of Microbiology and Immunology, Center fo
Author Info: (1) Department of Microbiology and Immunology, Center for Immunology, University of Minnesota, Minneapolis, MN, 55455, USA. (2) Department of Microbiology and Immunology, Center for Immunology, University of Minnesota, Minneapolis, MN, 55455, USA. (3) Department of Microbiology and Immunology, Center for Immunology, University of Minnesota, Minneapolis, MN, 55455, USA. (4) Department of Microbiology and Immunology, Center for Immunology, University of Minnesota, Minneapolis, MN, 55455, USA. (5) Department of Microbiology and Immunology, Center for Immunology, University of Minnesota, Minneapolis, MN, 55455, USA. (6) Department of Microbiology and Immunology, Center for Immunology, University of Minnesota, Minneapolis, MN, 55455, USA. (7) Department of Laboratory Medicine and Pathology, Center for Immunology, University of Minnesota, Minneapolis, MN, 55455, USA. (8) Department of Pediatrics, Center for Immunology, University of Minnesota, Minneapolis, MN, 55455, USA. (9) Department of Neurosurgery, University of Minnesota, Minneapolis, MN, 55455, USA. (10) Department of Obstetrics, Gynecology and Women's Health, University of Minnesota, Minneapolis, MN, 55455, USA. (11) Department of Microbiology and Immunology, Center for Immunology, University of Minnesota, Minneapolis, MN, 55455, USA. (12) Department of Microbiology and Immunology, Center for Immunology, University of Minnesota, Minneapolis, MN, 55455, USA. masopust@umn.edu.
