(1) Yu CF (2) Chang CH (3) Wang CC (4) Hong JH (5) Chiang CS (6) Chen FH

International journal of molecular sciences

Radiation therapy (RT) recruits myeloid cells, leading to an immunosuppressive microenvironment that impedes its efficacy against tumors. Combination of immunotherapy with RT is a potential approach to reversing the immunosuppressive condition and enhancing tumor control after RT. This study aimed to assess the effects of local interleukin-12 (IL-12) therapy on improving the efficacy of RT in a murine prostate cancer model. Combined treatment effectively shrunk the radioresistant tumors by inducing a T helper-1 immune response and influx of CD8+ T cells. It also delayed the radiation-induced vascular damage accompanied by increased _-smooth muscle actin-positive pericyte coverage and blood perfusion. Moreover, RT significantly reduced the IL-12-induced levels of alanine aminotransferase in blood. However, it did not further improve the IL-12-induced anti-tumor effect on distant tumors. Upregulated expression of T-cell exhaustion-associated genes was found in tumors treated with IL-12 only and combined treatment, suggesting that T-cell exhaustion is potentially correlated with tumor relapse in combined treatment. In conclusion, this study illustrated that combination of radiation and local IL-12 therapy enhanced the host immune response and promoted vascular maturation and function. Furthermore, combination treatment was associated with less systemic toxicity than IL-12 alone, providing a potential option for tumor therapy in clinical settings.

Author Info: (1) Radiation Biology Research Center, Institute for Radiological Research, Chang Gung Memorial Hospital Linkou Branch, Chang Gung University, Taoyuan 33302, Taiwan. Department of

Author Info: (1) Radiation Biology Research Center, Institute for Radiological Research, Chang Gung Memorial Hospital Linkou Branch, Chang Gung University, Taoyuan 33302, Taiwan. Department of Radiation Oncology, Chang Gung Memorial Hospital Linkou Branch, Taoyuan 33382, Taiwan. (2) Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 30013, Taiwan. (3) Radiation Biology Research Center, Institute for Radiological Research, Chang Gung Memorial Hospital Linkou Branch, Chang Gung University, Taoyuan 33302, Taiwan. Department of Radiation Oncology, Chang Gung Memorial Hospital Linkou Branch, Taoyuan 33382, Taiwan. Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan 33302, Taiwan. (4) Radiation Biology Research Center, Institute for Radiological Research, Chang Gung Memorial Hospital Linkou Branch, Chang Gung University, Taoyuan 33302, Taiwan. Department of Radiation Oncology, Chang Gung Memorial Hospital Linkou Branch, Taoyuan 33382, Taiwan. Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan 33302, Taiwan. (5) Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 30013, Taiwan. Institute of Nuclear Engineering and Science, National Tsing Hua University, Hsinchu 30013, Taiwan. Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 30013, Taiwan. (6) Radiation Biology Research Center, Institute for Radiological Research, Chang Gung Memorial Hospital Linkou Branch, Chang Gung University, Taoyuan 33302, Taiwan. Department of Radiation Oncology, Chang Gung Memorial Hospital Linkou Branch, Taoyuan 33382, Taiwan. Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan 33302, Taiwan.

Citation: Int J Mol Sci 2021 Sep 17 22: Epub09/17/2021

Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/34576217

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