The Change of Tumor Microenvironment in Residual Murine Glioma Following Radiation Therapy

Most patients (~ 90%) with malignant gliomas receive radiotherapy (RT) at some stage of their disease, but relative high percentage of patients still suffers from the residual brain tumor and disease recurrences. Our past researches on murine prostate cancers have discovered a hypoxia preferring macrophages in irradiated tumors. This particular subtype of macrophages can migrate to the hypoxic regions of RT-disturbed tumor microenvironments and is responsible for the resistance of prostate cancer to 2nd treatment. Despite many studies aiming to improve the efficacy of brain tumor radiotherapy, the alteration of the brain tumor microenvironments after RT has not been well established. In this proposal, we will use two murine brain tumor cell lines, one of them, ALTS1C1, established by one Co-PI (Prof. Chi-Shiun Chiang), to illustrate the change of brain tumor microenvironments following RT and how this is associated with the success of brain tumor therapy. This study does not only extend our understanding on the brain tumor microenvironments, but will also clarify the roles of microglia/macrophage in recurrent tumors. The success of this proposal will illustrate the potential of modulating TAM as a new approach to enhance the efficacy of cancer radiotherapy for brain tumors. To achieve the goal, three specific aims are planned. They are: 1. To dissect the dynamic relationships among tumor vascularity, hypoxia, and TAM in brain tumor after radiation therapy. 2. To identify the origins of brain TAM using GFP-tagged bone marrow derived-monocytes. 3. To study the brain tumor bed effect.

Project ID:PC10008-0627
External Project ID:NSC100-2314-B182A-094