Education

• MD (2003); Keio University School of Medicine, Tokyo, Japan
• Residency in internal medicine (2003-2005), Keio University Hospital, Tokyo, Japan
• PhD in medicine (2013); Keio University School of Medicine, Tokyo, Japan

Professional Experiences

• Senior Lecturer, Department of Immunology and Genomic Medicine, Center for Cancer Immunotherapy and Immunobiology (CCII)

Research Focus

Although recent cancer immunotherapies including PD-1 blockade have shown durable clinical effects in patients with various cancers, the efficacy is still limited to only a subset of patients. Pre-treatment immune status in tumor microenvironments varies among cancer patients and shows association with their prognoses and responses to various cancer therapies. We have revealed immunological subtypes of various cancers and identified various chemicals and antibodies capable of enhancing anti-tumor immunity using mouse tumor models including newly developed humanized mice. Their targets include other immune checkpoint molecules, oncogenic signals such as β-catenin, lipid metabolism pathways both in cancer cells and immune cells in cancer microenvironments.

Recently, we are using a variety of new technologies such as single cell RNA sequence, metabolite analyses, and spatial protein and gene analyses for the evaluation of immunologic characteristics of various human cancers such as lung cancer, renal cell carcinoma, and gastrointestinal cancer. We also investigate the effect of cellular stress responses in tumor microenvironment on anti-tumor immune responses including T cell memory formation.

Selected Publications

Chamoto, K., Yaguchi, T., Tajima, M. et al. Insights from a 30-year journey: function, regulation and therapeutic modulation of PD1. Nat Rev Immunol (2023). DOI: https://doi.org/10.1038/s41577-023-00867-9

Kato, Y., Yaguchi, T., Kubo, A., Iwata, T., Morii, K., Kato, D., Ohta, S., Satomi, R., Yamamoto, Y., Oyamada, Y., Ouchi, K., Takahashi, S., Ishioka, C., Matoba, R., Suematsu, M., Kawakami, Y. Inhibition of stearoyl-CoA desaturase 1（SCD1）enhances the antitumor T cell response through regulating β-catenin signaling in cancer cells & ER stress in T cells & synergizes with anti-PD-1 antibody. J Immunother Cancer. 10 e004616 (2022). DOI: 10.1136/jitc-2022-004616

Kinoshita, T., Sayem, MA., Yaguchi, T., Kharma, B., Morii, K., Kato, D., Ohta, S., Mashima, Y., Asamura H., Kawakami, Y.. Inhibition of vascular adhesion protein-1 enhances the anti-tumor effects of immune checkpoint inhibitors. Cancer Sci . 112: 1390-1401 (2021). DOI: 10.1111/cas.14812

Hayakawa, T., Yaguchi, T., Kawakami, Y. Enhanced anti-tumor effects of the PD-1 blockade combined with a highly absorptive form of curcumin targeting STAT3 Cancer sci 111: 4326-4335 (2020). DOI: 10.1111/cas.14675

Kato, D., Yaguchi, T., Iwata, T., Katoh, Y., Morii, K., Tsubota, K., Takise, Y., Tamiya, M., Kamada, H., Akiba, H., Tsumoto, K., Serada, S., Naka, T., Nishimura, R., Nakagawa, T., Kawakami, Y. GPC1 Specific CAR-T Cells Eradicate Established Solid Tumor Without Adverse Effects & Synergize With anti-PD-1 Ab. Elife. 9:e49392 (2020). DOI: 10.7554/eLife.49392

Yaguchi, T., Kobayashi, A., Inozume, T., Morii, K., Nagumo, H., Nihio, H., Iwata, T., Ka, Y., Katano, I., Ito, R., Ito, M., Kawakami, Y. et al. Human PBMC-transferred murine MHC class I / II-deficient NOG mice enable long-term evaluation of human immune responses. Cell Mol Immunol. 15: 953-962 (2018). DOI: https://doi.org/10.1038/cmi.2017.106

Nakamura, K., Yaguchi, T., Ohmura, G., Kobayashi, A., Kawamura, N., Iwata, T., Kiniwa, Y., Okuyama, R., Kawakami, Y. Involvement of local renin-angiotensin system in immunosuppression of tumor microenvironment. Cancer Sci. 109: 54-64 (2018). DOI: 10.1111/cas.13423

Inozume, T., Yaguchi, T., Furuta, F., Harada, K., Kawakami, Y., Shimada, S. Melanoma cells control anti-melanoma CTL responses via interaction between TIGIT & CD155 in the effector phase. J Invest Dermatol. 136: 255-63 (2016). DOI: 10.1038/JID.2015.404

Kinoshita, T., Muramatsu, R., Fujita, T., Nagumo, H., Sakurai, T., Noji, S., Takahata, E., Yaguchi, T., Tsukamoto, N., Kudo-Saito, C., Hayashi, Y., Kamiyama, I., Ohtsuka, T., Asamura, H., Kawakami, Y. Prognostic value of tumor-infiltrating lymphocytes differs depending on histological type & smoking habit in completely resected non-small-cell lung cancer. Ann Oncol. 27: 2117-2123 (2016). DOI: 10.1093/annonc/mdw319

Yaguchi, T., Goto, Y., Kido, K., Mochimaru, H., Sakurai, T., Tsukamoto, N., Kudo-Saito, C., Fujita, T., Sumimoto, H., Kawakami, Y. Immune Suppression & Resistance Mediated by Constitutive Activation of Wnt/β-Catenin Signaling in Human Melanoma Cells. J. Immunol 189: 2110-2117 (2012). DOI: 10.4049/jimmunol.1102282