Research and Education

Clinical application of cancer immunotherapy has demonstrated that “resurgence” of immune surveillance is achievable in humans. However, it has also been uncovered that the resurgence of immune surveillance is affected by environmental factors, such as energy and substance metabolism, in addition to genetic diversity on the cancer side and on the host side. We elucidate the regulatory mechanisms of immune tolerance and immune surveillance by integrating immunology, genomic medicine, metabolism, and bioinformatics. We investigate molecular expression and spatio-temporal dynamic changes of individual immune cells at the single-cell level and link the changes in intercellular networks to understanding from a macrobiological perspective at the tissue/individual level. To this end, we conduct integrated research using genetically-engineered mice that can track and examine each immune cell population based on the results of cancer patients. In addition, through the AMED Moonshot Project, we elucidate the dynamics of immune responses during the process, in which normal tissue cells acquire somatic mutations and become “cancerous” due to chronic inflammation and expand the project to preventive medicine.

　 The system and research equipment for conducting research of cancer cells and immune cells at the single-cell level (immune-genomic analysis). Also, an introduction of some of the research results to date.

Summary of the AMED Moonshot Project, which aims for a cancer-free society through cancer prevention.

Recet Publications

1. Kumagai S, Itahashi K, Nishikawa H: Regulatory T cell-mediated immunosuppression orchestrated by cancer: towards an immuno-genomic paradigm for precision medicine. Nat Rev Clin Oncol. 21(5):337-353. 2024.
2. Itahashi K, Irie T, Yuda J, Kumagai S, Tanegashima T, Lin Y-Z, Watanabe S, Goto Y, Suzuki J, Aokage K, Tsuboi M, Minami Y, Ishii G, Ohe Y, Ise W, Kurosaki T, Suzuki Y, Koyama S, Nishikawa H: BATF epigenetically and transcriptionally controls the activation program of regulatory T cells in human tumors. Sci Immunol 14;7(76):eabk0957 2022
3. Kumagai S, Koyama S, Itahashi K, Tanegashima T, Lin, Y-T, Togashi Y, Kamada T, Irie T, Okumura G, Kohno H, Ito D, Fujii R, Watanabe S, Sai A, Fukuoka S, Sugiyama E, Watanabe G, Owari T, Nishinakaumra H, Sugiyama D, Maeda Y, Kawazoe A, Yukami H, Cida K, Ohara Y, Yoshida T, Shinno Y, Takeyasu Y, Shirasawa M, Nakama K, Aokage K, Suzuki J, Ishii G, Kuwata T, Sakamoto N, Kawazu M, Ueno T, Mori T, Yamazaki N, Tsuboi M, Yatabe Y, Kinoshita T, Doi T, Shitara K, Mano H, Nishikawa H: Lactic acid promotes PD-1 expression in regulatory T cells in highly glycolytic tumor microenvironments. Cancer Cell. 40(2):201-218.e9 2022.
4. Kumagai　S, Togashi Y, Kamada T, Sugiyama E, Nishinakaumra H, Takeuchi Y, Kochin, V, Itahashi K, Maeda Y, Matsui S, Shibahara,T, Yamashita Y, Irie T, Tsuge A, Fukuoka S, Kawazoe A, Udagawa H, Kirita K, Aokage K, Ishii G, Kuwata T, Nakama K, Kawazu M, Ueno T, Yamazaki N, Goto K, Tsuboi M, Mano H, Doi T, Shitara K, Nishikawa H: The PD-1 expression balance between effector and regulatory T cell predicts the clinical efficacy of PD-1 blockade therapies. Nat Immunol. 21(11):1346-1358 2020.
5. Kumagai　S, Togashi Y, Sakai C, Kawazoe A, Kawazu M, Ueno T, Sato E, Kuwata T, Kinoshita T, Yamamoto M, Nomura S, Tsukamoto T, Mano H, Shitara K, Nishikawa H: An oncogenic alteration creates a tumor microenvironment that promotes tumor progression by conferring a metabolic advantage to regulatory T cells. Immunity. 53(1):187-203.e8 2020.

Laboratory

Professor: Hiroyoshi Nishikawa
Program Specific Professor: Takuma Kato
Associate Professor: Seo Wooseok
Assistant Professor: Shinichiro Kato
Program Specific Assistant Professor: Takashi Mikami

URL：https://www.ccii.med.kyoto-u.ac.jp/en/research/divisions-labs/division-of-cancer-immune-multicellular-system-regulation/