Immuno-Oncology, Autoimmune Diseases, Chronic Viral Infections
Immuno-Oncology (Exhausted CD8 T cells in Cancers)
Our research team have extensively studied the heterogeneity within the exhausted CD8 T-cell population in various types of cancers. We recently suggested the heterogeneity of exhausted tumor-infiltrating CD8 T cells based on differential PD-1 expression and its clinical implications in hepatocellular carcinoma patients. .
In this study, we suggested that combination therapy with anti-PD-1 and anti-Tim-3 and/or anti-Lag-3 further restored effector functions of exhausted CD8 T cells, providing evidence for designing novel immunotherapies with combined immune checkpoint blockades (Gastroenterology 2018).
Moreover, my research group investigated the roles of 4-1BB in exhausted CD8 T cells in the setting of tumor reactivity and activation of tumor-specific T cells in the tumor microenvironment, and found that 4-1BB co-stimulation further enhanced anti-PD-1-mediated reinvigoration of exhausted CD8 T cells from primary and metastatic sites of multiple cancers (Hepatology 2020; Journal for ImmunoTherapy of Cancer 2020).
Based on these studies, my research group is currently studying the anti-cancer effects of a novel bi-specific antibody targeting PD-L1 and 4-1BB, in collaboration with a biotechnology company (Journal for ImmunoTherapy of Cancer 2021)
Additionally, we have recently published a paper implicating CD69+CD103+ tissue-resident-like CD8 T cells as a potential immunotherapeutic target for cholangiocarcinoma (Liver International 2021)
Based on these studies, we are currently invetigating the roles of various immune cells such as CD8 T cells, CD4 T cells, and regulatory T cells in tumor microenvironment using human clinical samples and cancer animal models, and are also trying to develop novel therapeutic strategies against cancers.
Recently, our research topics have been expanded to the field of autoimmune diseases to investigate mechanisms related to immunopathology of autoimmune diseases such as alopecia areata and its accociated diseases.
We found that a novel CD8 T cell subpopulation originated from virtual memory CD8 T cells causes alopecia areta by TCR-independent cytotoxicity mechanism. We will conduct an in-depth immunological study to find development mechanism and detailed effector functions of this novel CD8 T cell subpopulation using various immunological assays such as multicolor FACS, single cell RNA sequencing and in vitro functional studies.
Chronic Viral Infections (Hepatitis C and B Viruses)
In the field of viral hepatitis, our lab has studied the effector functions of HCV-specific exhausted CD8 T cells following successful IFN-free therapy in patients with chronic hepatitis C (Journal of Infectious Diseases 2019).
We are studying ditinct immunological characteristics of CD8 T cells, MAIT cells, regulatory T cells and other immune cells in patients with chronic viral hepatitis virus infections. Ultimately, we are trying to develop novel therapeutic strategies and preventive vaccines against hepatitis C virus infestions.