Impact of tumor microenvironment on oncolytic viral therapy |
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| Authors: | Jeffrey Wojton Balveen Kaur |
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| Institution: | 1. Dardinger Laboratory for Neuro-oncology and Neurosciences, Department of Neurological Surgery, James Comprehensive Cancer Center and The Ohio State University Medical Center, Columbus, OH, United States;2. Neuroscience Graduate Studies Program, The Ohio State University Medical Center, Columbus, OH 43210, United States;1. Department of Surgery, City of Hope National Medical Center, Duarte, CA 91010, USA;1. Center for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ONT, Canada;2. Department of Biochemistry, Immunology and Microbiology, University of Ottawa, Ottawa, ONT, Canada;1. Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, Alabama, USA;2. Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama, USA;3. Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama, USA;4. School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama, USA;5. Department of Medicine, Division of Preventative Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA;6. AK Statistics, Bavaria, Germany;7. Institute of Medical Microbiology, University Hospital of Friedrich-Schiller-University, Jena, Germany;8. Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama, USA;9. Department of Pathology, Division of Anatomic Pathology, The University of Utah, Salt Lake City, Utah, USA;10. Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA;11. Department of Radiation Oncology, University of Chicago, Chicago, Illinois, USA;12. Department of Radiation Oncology, University of Alabama at Birmingham, Birmingham, Alabama, USA;1. Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada;1. Biodesign Center for Immunotherapy, Vaccines, and Virotherapy (B-CIVV), The Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA |
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| Abstract: | Interactions between tumor cells and their microenvironment have been shown to play a very significant role in the initiation, progression, and invasiveness of cancer. These tumor–stromal interactions are capable of altering the delivery and effectiveness of therapeutics into the tumor and are also known to influence future resistance and re-growth after treatment. Here we review recent advances in the understanding of the tumor microenvironment and its response to oncolytic viral therapy. The multifaceted environmental response to viral therapy can influence viral infection, replication, and propagation within the tumor. Recent studies have unveiled the complicated temporal changes in the tumor vasculature post-oncolytic virus (OV) treatment, and their impact on tumor biology. Similarly, the secreted extracellular matrix in solid tumors can affect both infection and spread of the therapeutic virus. Together, these complex changes in the tumor microenvironment also modulate the activation of the innate antiviral host immune response, leading to quick and efficient viral clearance. In order to combat these detrimental responses, viruses have been combined with pharmacological adjuvants and “armed” with therapeutic genes in order to suppress the pernicious environmental conditions following therapy. In this review we will discuss the impact of the tumor environment on viral therapy and examine some of the recent literature investigating methods of modulating this environment to enhance oncolysis. |
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