Immunotherapy has become a highly promising approach for cancer treatment. The immune system is evolved as a mechanism that detects and attacks foreign substances, such as microbial pathogens. On the other hand, the immune system does not attack cells or tissues of our body, which is the so-called immune tolerance. Cancer cells accumulate genetic mutations, making them different from normal cells. However, because the differences between cancer cells and normal cells are small, the immune system is usually tolerant to the cancer cells and does not mount strong responses to attack them. The general principle of tumor immunotherapy is to stimulate the tumor-specific T-cell responses strongly e...

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Immunotherapy has become a highly promising approach for cancer treatment. The immune system is evolved as a mechanism that detects and attacks foreign substances, such as microbial pathogens. On the other hand, the immune system does not attack cells or tissues of our body, which is the so-called immune tolerance. Cancer cells accumulate genetic mutations, making them different from normal cells. However, because the differences between cancer cells and normal cells are small, the immune system is usually tolerant to the cancer cells and does not mount strong responses to attack them. The general principle of tumor immunotherapy is to stimulate the tumor-specific T-cell responses strongly enough to overcome the tolerance. One way to boost antitumor T cell responses is to target negative regulators of T cell activation. This research project is to study the signaling mechanism that regulates the activation and function of CD8+ T cells, which is the central player of anticancer immunity. We have identified an enzyme that cleaves ubiquitin chains and regulates the signal transduction involved in CD8 T cell activation and anticancer function. Based on our preliminary studies, we believe that targeting this protein is an important approach to improve the efficacy of cancer immunotherapy. We will examine our hypothesis by performing a series of studies using both molecular biological tools and animal models of cancer immunotherapy. The outcome of these studies will be highly important for designing more effective approaches in cancer immunotherapy.

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