Center for Cancer Immunotherapy and Immunobiology

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  5. Professor Kenji Chamoto

Professor Kenji Chamoto
Department of Immunology and Genomic Medicine

Education

  • 2006: Graduated from the Department of Disease Control, Graduate School of Medicine, Hokkaido University, PhD course

Professional Experiences

  • 2006-2010: Assistant Professor, Institute for Genetic Medicine, University of Tsukuba
  • 2010-2011: Postdoc, Harvard Medical School, Brigham and Womens Hospital, MA, USA
  • 2011-2015: Postdoc, Ontario Cancer Institute/ Princess Margaret Cancer Center, ON, Canada
  • 2015-2016: Assistant Professor, Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University
  • 2016: Lecturer, Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University
  • 2018~: Associate Professor (concurrent position), Department of Immunology and Genomic Medicine, Center for Cancer Immunotherapy and Immunology (CCII), Graduate School of Medicine, Kyoto University
  • 2023~: Professor, Cancer Immunology PDT Research Department, Graduate School of Medicine, Kyoto University

Research Focus

The immune surveillance mechanism is responsible for monitoring cancer development, and for reactivating it through PD-1 blockade antibody which has been proven to be a game-changer in cancer treatment. However, a substantial number of patients remain unresponsive and autoimmune-like side effects have risen as an issue. The complexity of regulating anti-tumor immunity, primarily through T cells, presents numerous challenges.

To better understand the intricate relationship between cancer and immunity, we are conducting cutting-edge research on immuno-metabolism, ageing and intestinal bacteria. By examining these interrelated fields from a holistic perspective, we aim to shed light on unresolved issues and pave the way for breakthroughs in cancer treatment.

Our previous research has revealed the potential of compounds that promote mitochondrial metabolism in T cells to enhance the anti-tumor effect of PD-1 blockade therapy. We have also identified the crucial role of mitochondria-centered metabolism, particularly fatty acid oxidation, in immune ageing and anti-tumor immunity.

Our ultimate objective is to translate these fundamental discoveries into clinical applications. To this end, we are conducting Translational Research (TR) to bridge the gap between basic science and clinical practice, as well as reverse TR (rTR) using clinical specimens. By exploring the complex relationship between cancer and immunity through multiple angles, we are dedicated to finding novel strategies for combating this devastating disease.

Honors & Awards

Selected Publications

Singh VP, Hirose S, Takemoto M, Farrag A M.A.S., Sato S, Honjo T, Chamoto K (Co-corresponding author), Uesugi M (Co-Corresponding author). Chemoproteomic Identification of Spermidine-Binding Proteins and Antitumor-Immunity Activators. (2024) J Am Chem Soc. in press.

Hayashi H, Chamoto K (Co-corresponding author), Hatae R, Kurosaki T, Togashi Y, Fukuoka K, Goto M, Chiba Y, Tomida S, Ota T, Haratani K, Takahama T, Tanizaki J, Yoshida T, Iwasa T, Tanaka K, Takeda M, Hirano T, Yoshida H, Ozasa H, Sakamori Y, Sakai K, Higuchi K, Uga H, Suminaka C, Hirai T, Nishio K, Nakagawa K, Honjo T. Soluble immune checkpoint factors reflect exhaustion of antitumor immunity and response to PD-1 blockade. (2024) J Clin Invest. 134(7):e168318. DOI: https://doi.org/10.1172/JCI168318

Chamoto K, Zhang B, Tajima M, Honjo T, Fagarasan S. Spermidine – an old molecule with a new age-defying immune function. (2023) Trends Cell Biol. S0962-8924(23)00166-6. DOI: https://doi.org/10.1016/j.tcb.2023.08.002

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

Tanaka, K., Chamoto, K. (Co-corresponding author), Saeki, S., Hatae, R., Ikematsu, Y., Sakai, K., Ando, N., Sonomura, K., Kojima, S., Taketsuna, M., Kim, YH., Yoshida, H., Ozasa, H., Sakamori, Y., Hirano, T., Matsuda, F., Hirai, T., Nishio, K., Sakagami, T., Fukushima, M., Nakanishi, Y., Honjo, T., Okamoto, I.. Combination bezafibrate & nivolumab treatment of patients with advanced non–small cell lung cancer. (2022) Sci Transl Med. 14 (675): eabq0021. DOI: https://doi.org/10.1126/scitranslmed.abq0021

Al-Habsi, M., Chamoto, K. (Co-corresponding author), Matsumoto, K., Nomura, N., Zhang, B., Sugiura, Y., Sonomura, K., Maharani, A., Nakajima, Y., Wu, Y., Nomura, Y., Menzies, R., Tajima, M., Kitaoka, K., Haku, Y., Delghandi, S., Yurimoto, K., Matsuda, F., Iwata, S., Ogura, T., Fagarasan, S., Honjo, T. Spermidine activates mitochondrial trifunctional protein & improves antitumor immunity in mice. (2022) Science. 28; 378 (6618): eabj3510. DOI: https://www.science.org/doi/abs/10.1126/science.abj3510

Akrami, M., Menzies, R., Chamoto, K. (Co-corresponding author), Miyajima, M., Suzuki, R., Sato, H., Nishii, A., Tomura, M., Fagarasan, S., Honjo, T. Circulation of gut-preactivated naïve CD8+ T cells enhances antitumor immunity in B cell-defective mice. (2020) Proc Natl Acad Sci U S A. 117(38):23674-23683. DOI: https://www.pnas.org/doi/full/10.1073/pnas.2010981117

Kumar, A., Chamoto, K. (Co-corresponding author), Chowdhury, PS., Honjo T. Tumors attenuating the mitochondrial activity in T cells escape from PD-1 blockade therapy. (2020) eLife. 9, e52330. DOI: https://doi.org/10.7554/eLife.52330

Hatae, R., Chamoto, K. (Co-corresponding author), Kim, YH., Sonomura, K., Taneishi, K., Kawaguchi, S., Yoshida, H., Ozasa, H., Sakamori, Y., Akrami, M., Fagarasan, S., Masuda, I., Okuno, Y., Matsuda, F., Hirai, T., Honjo, T. Combination of host immune metabolic biomarkers for the PD-1 blockade cancer immunotherapy (2020) JCI insight, 5, e133501. https://insight.jci.org/articles/view/133501

Chowdhury, PS., Chamoto, K. (Co-corresponding author), Kumar, A., Honjo, T. PPAR-induced fatty acid oxidation in T cells increases the number of tumor-reactive CD8+ T cells & facilitates anti–PD-1 therapy. (2018) Cancer Immunol Res, 6: 1375-1387. DOI: https://doi.org/10.1158/2326-6066.CIR-18-0095

Chamoto, K., Chowdhury, PS., Kumar, A., Sonomura, K., Matsuda, F., Fagarasan, S., Honjo, T. Mitochondrial activation chemicals synergize with surface receptor PD-1 blockade for T cell-dependent antitumor activity. (2017) Proc Natl Acad Sci U S A. 114: E761-E770. DOI: 10.1073/pnas.1620433114

Chamoto, K., Guo, T., Imataki, O., Tanaka, M., Nakatsugawa, M., Ochi, T., Yamashita, Y., Saito, AM., Saito, TI., Butler, MO., Hirano, N. CD3b sequence motifs regulate autoreactivity of human invariant NKT cell receptors. (2016) J Autoimmun 68:39-51.

Takeshima, T., Chamoto, K. (Co-corresponding author), Wakita, D., Ohkuri, T., Togashi, Y., Shirato, H., Kitamura, H., Nishimura, T. Local Radiation Therapy Inhibits Tumor Growth through the Generation of Tumor-Specific CTL: Its Potentiation by Combination with Th1 Cell Therapy. (2010) Cancer Res. 70: 2697-706. DOI: 10.1158/0008-5472.CAN-09-2982

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