Modulating Anti-Cancer Immune Response by Radiation

  • Wang, Chun-Chieh (PI)
  • Chen, Fang-Hsin (CoPI)

Project: National Science and Technology CouncilNational Science and Technology Council Academic Grants

Project Details

Abstract

Radiotherapy is one of the mainstay modalities for cancer treatment. The anti-cancer effect of radiotherapy was believed to depend on the radiation-induced DNA damage, which killed cancer cells. However, more and more studies support that not only the cytocidal effect, but also the responses of the tumor microenvironment and tumor-infiltrating immune cells determine the treatment outcome. Recently, the discovery of immune "checkpoint" significantly promotes the anti-tumor efficacies of immunotherapy. These anti-checkpoint therapies reverse the immune tolerance of cancer cells and control the tumor growth. There is still controversial about the impact of radiation on the immune response. Radiation kills the sensitive lymphocytes and induces some immunosuppressive responses. In contrast, radiation could promotes the immunogenic cell death to stimulate the dendritic cells presenting tumor antigens to the effecter cells, which kill tumor cells and inhibit tumor regrowth. This anti-cancer effect could occur outside the irradiated region, which is called “abscopal effect”. This two-year project will explore the effects of radiation on the local immune response and the development of abscopal effect. To study the local effect, we will use the GFP-expressing immune cells within the window chamber to measure the effects of single and fractionated radiation on these cells. Furthermore, how local radiation affects the function of the antigen-presenting cells, dendritic cells, will be explored in this project. To study the abscopal effect, we will set up an abscopal effect model by irradiating the tumor over the hind leg of the mouse and observing the non-irradiated tumor within the window chamber. By adjusting the dose and schedule of irradiation or giving immune-modulating agents will be tried to optimize the abscopal effect. The results of this project can be utilized as an experimental model for further studies combining the immunotherapy and radiotherapy. Although abscopal effect is hardly seen by radiation alone, there are many clinical reports when combining radiotherapy and immunotherapy. Data from the fractionated irradiation could be used to optimize the treatment schedule of radiotherapy to improve the local and distal tumor control.

Project IDs

Project ID:PC10701-0985
External Project ID:MOST106-2314-B182-020-MY2
StatusFinished
Effective start/end date01/08/1831/07/19

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