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
External Project ID:MOST106-2314-B182-020-MY2
Status | Finished |
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Effective start/end date | 01/08/18 → 31/07/19 |
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