Based on the hypothesis that early disease treatment will be a more effective immunotherapy strategy, Bourgeois-Daigneault et al. demonstrated the long-term protective impact of the oncolytic Maraba virus delivered as neoadjuvant therapy to mice bearing syngeneic TNBC tumors. Gene expression and secreted cytokine analysis of infected tumor cells demonstrated upregulation of key inflammatory pathways, including PD-L1. Treatment with anti-PD-1 and anti-CTLA-4 post-surgery dramatically improved overall survival following rechallenge.
Triple-negative breast cancer (TNBC) is an aggressive disease for which treatment options are limited and associated with severe toxicities. Immunotherapeutic approaches like immune checkpoint inhibitors (ICIs) are a potential strategy, but clinical trials have demonstrated limited success in this patient cohort. Clinical studies using ICIs have revealed that patients with preexisting anticancer immunity are the most responsive. Given that oncolytic viruses (OVs) induce antitumor immunity, we investigated their use as an ICI-sensitizing approach. Using a therapeutic model that mimics the course of treatment for women with newly diagnosed TNBC, we demonstrate that early OV treatment coupled with surgical resection provides long-term benefits. OV therapy sensitizes otherwise refractory TNBC to immune checkpoint blockade, preventing relapse in most of the treated animals. We suggest that OV therapy in combination with immune checkpoint blockade warrants testing as a neoadjuvant treatment option in the window of opportunity between TNBC diagnosis and surgical resection.
Author Info: (1) Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa K1H 8L6, Canada. mbourgeois@ohri.ca jbell@ohri.ca. Department of Biochemistry, Microbiology an
Author Info: (1) Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa K1H 8L6, Canada. mbourgeois@ohri.ca jbell@ohri.ca. Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa K1H 8M5, Canada. (2) Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa K1H 8L6, Canada. Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa K1H 8M5, Canada. (3) Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa K1H 8L6, Canada. Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa K1H 8M5, Canada. (4) Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa K1H 8L6, Canada. Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa K1H 8M5, Canada. (5) Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa K1H 8L6, Canada. Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa K1H 8M5, Canada. (6) Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa K1H 8L6, Canada. Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa K1H 8M5, Canada. (7) Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa K1H 8L6, Canada. (8) Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa K1H 8L6, Canada. (9) Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa K1H 8L6, Canada. Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa K1H 8M5, Canada. (10) Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton L8S 4K1, Canada. (11) Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa K1H 8M5, Canada. Children's Hospital of Eastern Ontario Research Institute, Ottawa K1H 8L1, Canada. (12) Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa K1H 8L6, Canada. (13) Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa K1H 8L6, Canada. Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa K1H 8M5, Canada. (14) Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa K1H 8L6, Canada. mbourgeois@ohri.ca jbell@ohri.ca. Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa K1H 8M5, Canada.
