Annual Report 2021

Division of Cancer Immunotherapy

Tetsuya Nakatsura, Yasushi Uemura, Keigo Saito, Manami Shimomura, Kyoko Fukuda, Nobuo Tsukamoto, Norihiro Fujinami, Arnaud Couzinet, Kazumasa Takenouchi, Kumiko Yamashima, Charneau Jimmy, Keigo Chida, Kayoko Shoda, Yukiko Kozaki, Karin Iwasa, Rieko Oki, Hiroki Kinoshita, Toshihiro Suzuki, Daiki Ikarashi, Masateru Yamamoto, Shoichi Mizuno, Megumi Ozaki

Introduction

 Our division aims to investigate evidenced-based cancer immunotherapy through repeated basic research and translational research. This division is focused on developing not only more effective immunotherapies but also immunological methods for the suppression of recurrence or for cancer prevention.

Research activities

1) Public research funds and joint research funds were constantly obtained, and many kinds of joint research with companies and academia were conducted.

2) Research aimed at clinical trials of personalized cancer vaccines is ongoing.

3) Personalized T cell therapy is being developed.

4) Research on circulating tumor cells in the blood is being conducted.

5) Research and development of a cell-mediated immunity test method for COVID-19 vaccines is being conducted.

6) Various immune cells derived from iPS cells for cancer treatment are being prepared, and their usefulness is being studied at the basic research level.

7) A Phase I clinical trial of FITC-CAR-T therapy targeting CD20 is being conducted in cooperation with Prof. Tamada at Yamaguchi University.

8) A Phase I clinical trial of iPS cell-derived CAR-ILC/NK cell therapy targeting GPC3 is being conducted in cooperation with Dr. Kaneko at Kyoto University’s CiRA.

9) We are engaged in development research aimed at clinical trials of novel CAR-T cell therapies.

Education

 Our division accepted and trained the following trainees: students on the doctoral course at the Graduate School of Medicine and Medical Doctors, students on the doctoral and masters courses at Tokyo University of Science, and residents and senior residents at NCCHE. A total of 5 doctoral course graduates (including 1 French person) and 1 master's course graduate were produced.

Future Prospects

 Immune checkpoint blockades like anti-PD-1 antibody or anti-PD-L1 antibody and CAR-T cell therapy targeting CD19 have shown high clinical effectiveness, so the development of innovative cancer immunotherapy is required. We will continue to undertake activities associated with bridging basic research and clinical application, aiming to develop novel immunotherapeutic methods.

List of papers published in 2021

Journal

1. Chida K, Kawazoe A, Suzuki T, Kawazu M, Ueno T, Takenouchi K, Nakamura Y, Kuboki Y, Kotani D, Kojima T, Bando H, Mishima S, Kuwata T, Sakamoto N, Watanabe J, Mano H, Ikeda M, Shitara K, Endo I, Nakatsura T, Yoshino T. Transcriptomic Profiling of MSI-H/dMMR Gastrointestinal Tumors to Identify Determinants of Responsiveness to Anti-PD-1 Therapy. Clinical cancer research: an official journal of the American Association for Cancer Research, 28:2110-2117, 2022

2. Yagi N, Suzuki T, Mizuno S, Kojima M, Kudo M, Sugimoto M, Kobayashi S, Gotohda N, Ishii G, Nakatsura T. Component with abundant immune-related cells in combined hepatocellular cholangiocarcinoma identified by cluster analysis. Cancer science, 113:1564-1574, 2022

3. Charneau J, Suzuki T, Shimomura M, Fujinami N, Mishima Y, Hiranuka K, Watanabe N, Yamada T, Nakamura N, Nakatsura T. Development of antigen-prediction algorithm for personalized neoantigen vaccine using human leukocyte antigen transgenic mouse. Cancer science, 113:1113-1124, 2022

4. Ikarashi D, Kitano S, Tsuyukubo T, Takenouchi K, Nakayama T, Onagi H, Sakaguchi A, Yamashita M, Mizugaki H, Maekawa S, Kato R, Kato Y, Sugai T, Nakatsura T, Obara W. Pretreatment tumour immune microenvironment predicts clinical response and prognosis of muscle-invasive bladder cancer in the neoadjuvant chemotherapy setting. British journal of cancer, 126:606-614, 2022

5. Aoki H, Ueha S, Nakamura Y, Shichino S, Nakajima H, Shimomura M, Sato A, Nakatsura T, Yoshino T, Matsushima K. Greater extent of blood-tumor TCR repertoire overlap is associated with favorable clinical responses to PD-1 blockade. Cancer science, 112:2993-3004, 2021

6. Chida K, Kawazoe A, Kawazu M, Suzuki T, Nakamura Y, Nakatsura T, Kuwata T, Ueno T, Kuboki Y, Kotani D, Kojima T, Taniguchi H, Mano H, Ikeda M, Shitara K, Endo I, Yoshino T. A Low Tumor Mutational Burden and PTEN Mutations Are Predictors of a Negative Response to PD-1 Blockade in MSI-H/dMMR Gastrointestinal Tumors. Clinical cancer research: an official journal of the American Association for Cancer Research, 27:3714-3724, 2021

7. Kudo-Saito C, Ogiwara Y, Imazeki H, Boku N, Uemura Y, Zhang R, Kawano-Nagatsuma A, Kojima M, Ochiai A. CD11b+DIP2Ab+LAG3b+ cells facilitate immune dysfunction in colorectal cancer. American journal of cancer research, 11:5428-5439, 2021

8. Sakaguchi A, Horimoto Y, Onagi H, Ikarashi D, Nakayama T, Nakatsura T, Shimizu H, Kojima K, Yao T, Matsumoto T, Ogura K, Kitano S. Plasma cell infiltration and treatment effect in breast cancer patients treated with neoadjuvant chemotherapy. Breast cancer research: BCR, 23:99, 2021

9. Ikarashi D, Okimoto T, Shukuya T, Onagi H, Hayashi T, Sinicropi-Yao SL, Amann JM, Nakatsura T, Kitano S, Carbone DP. Comparison of Tumor Microenvironments Between Primary Tumors and Brain Metastases in Patients With NSCLC. JTO clinical and research reports, 2:100230, 2021

10. Nosaka K, Suzuki S, Yoshikawa T, Shimomura M, Kitami K, Yoshida K, Yoshihara M, Kikkawa F, Nakatsura T, Kajiyama H. Heat Shock Protein 105 as an Immunotherapeutic Target for Patients With Cervical Cancer. Anticancer research, 41:4741-4751, 2021

11. Charneau J, Suzuki T, Shimomura M, Fujinami N, Nakatsura T. Peptide-Based Vaccines for Hepatocellular Carcinoma: A Review of Recent Advances. Journal of hepatocellular carcinoma, 8:1035-1054, 2021

12. Zhang R, Liu T, Tsuchiya N, Mashima H, Kobayashi T, Nakatsura T, Ohdan H, Endo I, Senju S, Uemura Y. Induced pluripotent stem cell-derived, genetically engineered myeloid cells as unlimited cell source for dendritic cell-related cancer immunotherapy. J Immunol Regen Med, 12:100042, 2021

13. Wang B, Iriguchi S, Waseda M, Ueda N, Ueda T, Xu H, Minagawa A, Ishikawa A, Yano H, Ishi T, Ito R, Goto M, Takahashi R, Uemura Y, Hotta A, Kaneko S. Generation of hypoimmunogenic T cells from genetically engineered allogeneic human induced pluripotent stem cells. Nature biomedical engineering, 5:429-440, 2021

14. Shen S, Wu Q, Liu J, Wu L, Zhang R, Uemura Y, Yu X, Chen L, Liu T. Analysis of human glioma-associated co-inhibitory immune checkpoints in glioma microenvironment and peripheral blood. International journal of immunopathology and pharmacology, 35:2.05874E+16, 2021

15. Aoki H, Ueha S, Shichino S, Ogiwara H, Shitara K, Shimomura M, Suzuki T, Nakatsura T, Yamashita M, Kitano S, Kuroda S, Wakabayashi M, Kurachi M, Ito S, Doi T, Matsushima K. Transient Depletion of CD4(+) Cells Induces Remodeling of the TCR Repertoire in Gastrointestinal Cancer. Cancer immunology research, 9:624-636, 2021