Kouji Matsushima

Division of Molecular Regulation of Inflammatory and Immune Diseases
Inflammation and Immunology

Research theme

  • Molecular and cellular bases for chronic inflammation-associated organ fibrosis
  • Clinical development of novel combination cancer immunotherapy
  • Molecular mechanisms underlying chronic rejection of allogeneic cell and organ transplantation

Selected publications:

  1. Sekido, N. et al. Prevention of lung reperfusion injury in rabbits by a monoclonal antibody against interleukin-8. Nature (1993). doi:10.1038/365654a0
  2. Wada, T. et al. Intervention of crescentic glomerulonephritis by antibodies to monocyte chemotactic and activating factor (MCAF/MCP-1). FASEB J. (1996).
  3. Yoneyama, H. et al. Pivotal Role of Dendritic Cell–derived CXCL10 in the Retention of T Helper Cell 1 Lymphocytes in Secondary Lymph Nodes. J. Exp. Med. (2002). doi:10.1084/jem.20011983
  4. Murai, M. et al. Peyer’s patch is the essential site in initiating murine acute and lethal graft-versus-host reaction. Nat. Immunol. (2003). doi:10.1038/ni879
  5. Hashimoto, S. I. et al. 5′-end SAGE for the analysis of transcriptional start sites. Nat. Biotechnol. (2004). doi:10.1038/nbt998
  6. Terashima, Y. et al. Pivotal function for cytoplasmic protein FROUNT in CCR2-mediated monocyte chemotaxis. Nat. Immunol. (2005). doi:10.1038/ni1222
  7. Sawanobori, Y. et al. Chemokine-mediated rapid turnover of myeloid-derived suppressor cells in tumor-bearing mice. Blood (2008). doi:10.1182/blood-2008-01-136895
  8. Yamamoto, K. et al. Phase I study of KW-0761, a defucosylated humanized anti-CCR4 antibody, in relapsed patients with adult T-cell leukemia-lymphoma and peripheral T-cell lymphoma. J. Clin. Oncol. (2010). doi:10.1200/JCO.2009.25.3575
  9. Shono, Y. et al. Bone marrow graft-versus-host disease: Early destruction of hematopoietic niche after MHC-mismatched hematopoietic stem cell transplantation. Blood (2010). doi:10.1182/blood-2009-11-253559
  10. Kurachi, M. et al. Chemokine receptor CXCR3 facilitates CD8 + T cell differentiation into short-lived effector cells leading to memory degeneration. J. Exp. Med. (2011). doi:10.1084/jem.20102101
  11. Tsukui, T. et al. Qualitative rather than quantitative changes are hallmarks of fibroblasts in bleomycin-induced pulmonary fibrosis. Am. J. Pathol. (2013). doi:10.1016/j.ajpath.2013.06.005
  12. Ueha, S. et al. Robust anti-tumor effects of combined anti-CD4 depleting antibody and anti-PD-1/PD-L1 immune checkpoint antibody treatment in mice. Cancer Immunol. Res. (2015). doi:10.1158/2326-6066.CIR-14-0190
  13. Shichino, S. et al. Reduced supply of monocyte-derived macrophages leads to a transition from nodular to diffuse lesions and tissue cell activation in silica-induced pulmonary fibrosis in mice. Am. J. Pathol. (2015). doi:10.1016/j.ajpath.2015.07.013
  14. Tsukui, T., Ueha, S., Shichino, S., Inagaki, Y. & Matsushima, K. Intratracheal cell transfer demonstrates the profibrotic potential of resident fibroblasts in pulmonary fibrosis. Am. J. Pathol. (2015). doi:10.1016/j.ajpath.2015.07.022
  15. Hashimoto, S. et al. Comprehensive single-cell transcriptome analysis reveals heterogeneity in endometrioid adenocarcinoma tissues. Sci. Rep. (2017). doi:10.1038/s41598-017-14676-3
  16. Chen CY, Ueha S, Ishiwata Y, Yokochi S, Yang D, Oppenheim JJ, Ogiwara H, Shichino S, Deshimaru S, Shand FH, Shibayama S, Matsushima K. Combined treatment with HMGN1 and anti-CD4 depleting antibody reverses T cell exhaustion and exerts robust anti-tumor effects in mice. J Immunother Cancer. 7(1):21, 2019.
  17. Aoki H, Ueha S, Shichino S, Ogiwara H, Hashimoto S, Kakimi K, Ito S, Matsushima K. TCR repertoire analysis reveals mobilization of novel CD8+ T cell clones into the Cancer-Immunity Cycle following anti-CD4 antibody administration. Front Immunol. 9:3185, 2019.
  18. Shichino S, Ueha S, Hashimoto S, Otsuji M, Abe J, Tsukui T, Deshimaru S, Nakajima T, Kosugi-Kanaya M, Shand FH, Inagaki Y, Shimano H, Matsushima K. Transcriptome network analysis identifies protective role of the LXR-SREBP-1c axis in murine pulmonary fibrosis. JCI Insight. 4(1):122163,2019.
  19. Shitara K, Ueha S, Shichino S, Aoki H, Ogiwara H, Nakatsura T, Suzuki T, Shimomura M, Yoshikawa T, Shoda K, Kitano S, Yamashita M, Nakayama T, Sato A, Kuroda S, Wakabayashi M, Nomura S, Yokochi S, Ito S, Matsushima K, Doi T. First-in-human phase 1 study of IT1208, a defucosylated humanized anti-CD4 depleting antibody, in patients with advanced solid tumors. J Immunother Cancer. 7(1):195, 2019.
  20. Terashima Y, Toda E, Itakura M, Otsuji M, Yoshinaga S, Kazuhiro Okumura K, Shand FH, Komohara Y, Takeda M, Kokubo K, Chen MC, Yokoi S, Rokutan H, Kofuku Y, Ohnishi K, Ohira M, Iizasa T, Nakano H, Okabe T, Kojima H, Shimizu A, Kanegasaki S, Zhang MR, Shimada I, Nagase H, Terasawa H, Matsushima K. Targeting FROUNT with disulfiram suppresses macrophage accumulation and tumor-promoting properties. Nat Commun. 11:609, 2020.