Translational Immunology

• 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.