Next Article in Journal
Antistress Action of Melanocortin Derivatives Associated with Correction of Gene Expression Patterns in the Hippocampus of Male Rats Following Acute Stress
Next Article in Special Issue
Inhibition of Wnt/β-Catenin Signaling Sensitizes Esophageal Cancer Cells to Chemoradiotherapy
Previous Article in Journal
The Impact of Gut Microbiota-Derived Metabolites in Autism Spectrum Disorders
Previous Article in Special Issue
Fractionated Irradiation of Right Thorax Induces Abscopal Damage on Bone Marrow Cells via TNF-α and SAA
Article

Local Interleukin-12 Treatment Enhances the Efficacy of Radiation Therapy by Overcoming Radiation-Induced Immune Suppression

1
Radiation Biology Research Center, Institute for Radiological Research, Chang Gung Memorial Hospital Linkou Branch, Chang Gung University, Taoyuan 33302, Taiwan
2
Department of Radiation Oncology, Chang Gung Memorial Hospital Linkou Branch, Taoyuan 33382, Taiwan
3
Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 30013, Taiwan
4
Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan 33302, Taiwan
5
Institute of Nuclear Engineering and Science, National Tsing Hua University, Hsinchu 30013, Taiwan
6
Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 30013, Taiwan
*
Authors to whom correspondence should be addressed.
Academic Editors: Melpo Christofidou-Solomidou and Michael Hausmann
Int. J. Mol. Sci. 2021, 22(18), 10053; https://doi.org/10.3390/ijms221810053
Received: 18 August 2021 / Revised: 11 September 2021 / Accepted: 16 September 2021 / Published: 17 September 2021
(This article belongs to the Special Issue Radiation Biology and Molecular Radiation Oncology)
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 α-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. View Full-Text
Keywords: radiation; prostate cancer; interleukin-12; T cell exhaustion; vascular maturation; liver toxicity radiation; prostate cancer; interleukin-12; T cell exhaustion; vascular maturation; liver toxicity
Show Figures

Figure 1

MDPI and ACS Style

Yu, C.-F.; Chang, C.-H.; Wang, C.-C.; Hong, J.-H.; Chiang, C.-S.; Chen, F.-H. Local Interleukin-12 Treatment Enhances the Efficacy of Radiation Therapy by Overcoming Radiation-Induced Immune Suppression. Int. J. Mol. Sci. 2021, 22, 10053. https://doi.org/10.3390/ijms221810053

AMA Style

Yu C-F, Chang C-H, Wang C-C, Hong J-H, Chiang C-S, Chen F-H. Local Interleukin-12 Treatment Enhances the Efficacy of Radiation Therapy by Overcoming Radiation-Induced Immune Suppression. International Journal of Molecular Sciences. 2021; 22(18):10053. https://doi.org/10.3390/ijms221810053

Chicago/Turabian Style

Yu, Ching-Fang, Chun-Hsiang Chang, Chun-Chieh Wang, Ji-Hong Hong, Chi-Shiun Chiang, and Fang-Hsin Chen. 2021. "Local Interleukin-12 Treatment Enhances the Efficacy of Radiation Therapy by Overcoming Radiation-Induced Immune Suppression" International Journal of Molecular Sciences 22, no. 18: 10053. https://doi.org/10.3390/ijms221810053

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop