Abstract
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 8 Gy treatment of MOC1ova cells compared to 2 Gy. 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, 8 Gy enhanced tumor cell susceptibility to T-lymphocyte killing to a greater degree than 2 Gy. Conclusion In the context of using clinically-relevant doses of radiation treatment as an adjuvant for immunotherapy, 8 Gy is superior to 2 Gy 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.
Original language | English (US) |
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Pages (from-to) | 87-94 |
Number of pages | 8 |
Journal | Oral Oncology |
Volume | 71 |
DOIs | |
State | Published - Aug 2017 |
Keywords
- Cytotoxic T-lymphocyte
- Immunity
- Radiation
- T-lymphocyte priming
- Tumor microenvironment
ASJC Scopus subject areas
- Oral Surgery
- Oncology
- Cancer Research