Dose-dependent enhancement of T-lymphocyte priming and CTL lysis following ionizing radiation in an engineered model of oral cancer.
- Resource Type
- Academic Journal
- Authors
- Morisada M; Translational Tumor Immunology Program, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD, United States.; Moore EC; Translational Tumor Immunology Program, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD, United States.; Hodge R; Translational Tumor Immunology Program, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD, United States.; Friedman J; Translational Tumor Immunology Program, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD, United States.; Cash HA; Translational Tumor Immunology Program, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD, United States.; Hodge JW; Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, United States.; Mitchell JB; Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, United States.; Allen CT; Translational Tumor Immunology Program, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD, United States; Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, MD, United States. Electronic address: clint.allen@nih.gov.
- Source
- Publisher: Elsevier Country of Publication: England NLM ID: 9709118 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0593 (Electronic) Linking ISSN: 13688375 NLM ISO Abbreviation: Oral Oncol Subsets: MEDLINE
- Subject
- Language
- English
Objectives: Determine if direct tumor cell cytotoxicity, antigen release, and susceptibility to T-lymphocyte killing following radiation treatment is dose-dependent.
Materials and Methods: Mouse oral cancer cells were engineered to express full-length ovalbumin as a model antigen. Tumor antigen release with uptake and cross presentation of antigen by antigen presenting cells with subsequent priming and expansion of antigen-specific T-lymphocytes following radiation was modeled in vitro and in vivo. T-lymphocyte mediated killing was measured following radiation treatment using a novel impedance-based cytotoxicity assay.
Results: Radiation treatment induced dose-dependent induction of executioner caspase activity and apoptosis in MOC1 cells. In vitro modeling of antigen release and T-lymphocyte priming demonstrated enhanced proliferation of OT-1 T-lymphocytes with 8Gy treatment of MOC1ova cells compared to 2Gy. This was validated in vivo following treatment of established MOC1ova tumors and adoptive transfer of antigen-specific T-lymphocytes. Using a novel impedance-based cytotoxicity assay, 8Gy enhanced tumor cell susceptibility to T-lymphocyte killing to a greater degree than 2Gy.
Conclusion: In the context of using clinically-relevant doses of radiation treatment as an adjuvant for immunotherapy, 8Gy is superior to 2Gy for induction of antigen-specific immune responses and enhancing tumor cell susceptibility to T-lymphocyte killing. These findings have significant implications for the design of trials combining radiation and immunotherapy.
(Published by Elsevier Ltd.)