Radiation and Anti-Tumor Immunity
Radiotherapy eliminates cancer cells by direct cytotoxicity. Preclinical and clinical data have shown that radiotherapy (RT) also acts as an immune modifier, suggesting that it could be utilized to boost anti-tumor immunity.
Radiation causes immunogenic cell death and releases autologous neoantigens to the immune system. Given many lines of evidence supporting the notion that RT may enrich tumor-specific effector lymphocytes and elicit the priming of systemic anti-tumor T cell responses, it would be reasonable to expect that this will contribute to the control of metastatic tumor growth after radiation. However, tumor remission outside the irradiated area, also known as an "abscopal effect", is rarely seen in the clinic using RT alone. These puzzling observations are likely the consequence of the complexity of immuno-suppressive effects caused by radiation on immune cells and on the tumor microenvironment.
My published studies have indicated a dysfunctional T cell state is triggered after radiation, including impaired T cell activation and metabolic reprogramming; elevated PD-1 expression in CD4+ and CD8+ T cells, and disturbed helper T cell differentiation.
My current research investigates the connection between post-radiation tumor microenvironment changes and anti- tumor immunity using animal models. Immune-focused transcriptomic and metabolomic analysis on tumor tissues are being carried out after radiation treatment.
TCR repertoire analysis is being used to assess tumor immunogenicity. The goal is to understand how combined radiotherapy and immunotherapy can achieve competent systemic immune responses against tumor.
