Tumor-derived semaphorin 4A improves PD-1–blocking antibody efficacy by enhancing CD8 <sup>+</sup> T cell cytotoxicity and proliferation

DOI Web Site 参考文献51件 オープンアクセス
  • Yujiro Naito
    Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
  • Shohei Koyama
    Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
  • Kentaro Masuhiro
    Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
  • Takashi Hirai
    Department of Immunopathology, World Premier International Research Center (WPI), Immunology Frontier Research Center (IFReC), Osaka University, Suita, Osaka, Japan.
  • Takeshi Uenami
    Department of Thoracic Oncology, National Hospital Organization, Osaka Toneyama Medical Center, Toyonaka, Osaka, Japan.
  • Takako Inoue
    Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, Japan.
  • Akio Osa
    Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
  • Hirotomo Machiyama
    Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
  • Go Watanabe
    Division of Cancer Immunology, Research Institute/Exploratory Oncology Research and Clinical Trial Center (EPOC), National Cancer Center, Kashiwa,Chiba, and Tokyo, Japan.
  • Nicolas Sax
    KOTAI Biotechnologies Inc., Suita, Osaka, Japan.
  • Jordan Villa
    KOTAI Biotechnologies Inc., Suita, Osaka, Japan.
  • Yumi Kinugasa-Katayama
    Department of Cellular Immunology, Research Institute for Microbial Diseases (RIMD), Osaka University, Suita, Osaka, Japan.
  • Satoshi Nojima
    Department of Pathology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
  • Moto Yaga
    Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
  • Yuki Hosono
    Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
  • Daisuke Okuzaki
    Single Cell Genomics, Human Immunology, WPI, IFReC, Osaka University, Suita, Osaka, Japan.
  • Shingo Satoh
    Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
  • Takeshi Tsuda
    Department of Otorhinolaryngology–Head and Neck Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
  • Yoshimitsu Nakanishi
    Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
  • Yasuhiko Suga
    Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
  • Takayoshi Morita
    Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
  • Kiyoharu Fukushima
    Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
  • Masayuki Nishide
    Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
  • Takayuki Shiroyama
    Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
  • Kotaro Miyake
    Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
  • Kota Iwahori
    Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
  • Haruhiko Hirata
    Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
  • Izumi Nagatomo
    Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
  • Yukihiro Yano
    Department of Thoracic Oncology, National Hospital Organization, Osaka Toneyama Medical Center, Toyonaka, Osaka, Japan.
  • Motohiro Tamiya
    Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, Japan.
  • Toru Kumagai
    Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, Japan.
  • Norihiko Takemoto
    Department of Otorhinolaryngology–Head and Neck Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
  • Hidenori Inohara
    Department of Otorhinolaryngology–Head and Neck Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
  • Sho Yamasaki
    Laboratory of Molecular Immunology, WPI, IFReC, Osaka University, Suita, Osaka, Japan.
  • Kazuo Yamashita
    KOTAI Biotechnologies Inc., Suita, Osaka, Japan.
  • Taiki Aoshi
    Department of Cellular Immunology, Research Institute for Microbial Diseases (RIMD), Osaka University, Suita, Osaka, Japan.
  • Esra A. Akbay
    Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Naoki Hosen
    Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University, Suita, Osaka, Japan.
  • Yasushi Shintani
    Department of General Thoracic Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
  • Hyota Takamatsu
    Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
  • Masahide Mori
    Department of Thoracic Oncology, National Hospital Organization, Osaka Toneyama Medical Center, Toyonaka, Osaka, Japan.
  • Yoshito Takeda
    Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
  • Atsushi Kumanogoh
    Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.

抄録

<jats:p> Immune checkpoint inhibitors (ICIs) have caused revolutionary changes in cancer treatment, but low response rates remain a challenge. Semaphorin 4A (Sema4A) modulates the immune system through multiple mechanisms in mice, although the role of human Sema4A in the tumor microenvironment remains unclear. This study demonstrates that histologically Sema4A-positive non–small cell lung cancer (NSCLC) responded significantly better to anti–programmed cell death 1 (PD-1) antibody than Sema4A-negative NSCLC. Intriguingly, SEMA4A expression in human NSCLC was mainly derived from tumor cells and was associated with T cell activation. Sema4A promoted cytotoxicity and proliferation of tumor-specific CD8 <jats:sup>+</jats:sup> T cells without terminal exhaustion by enhancing mammalian target of rapamycin complex 1 and polyamine synthesis, which led to improved efficacy of PD-1 inhibitors in murine models. Improved T cell activation by recombinant Sema4A was also confirmed using isolated tumor-infiltrating T cells from patients with cancer. Thus, Sema4A might be a promising therapeutic target and biomarker for predicting and promoting ICI efficacy. </jats:p>

収録刊行物

  • Science Advances

    Science Advances 9 (20), 2023-05-19

    American Association for the Advancement of Science (AAAS)

参考文献 (51)*注記

もっと見る

関連プロジェクト

もっと見る

詳細情報 詳細情報について

問題の指摘

ページトップへ