Docetaxel Upregulates HMGB1 Levels in Non-small Cell Lung Cancer

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  • Haruna Miya
    Shionogi Co., Ltd. Department of Clinical Research in Tumor Immunology, Osaka University Graduate School of Medicine
  • Hirata Michinari
    Shionogi Co., Ltd. Department of Clinical Research in Tumor Immunology, Osaka University Graduate School of Medicine
  • Iwahori Kota
    Department of Clinical Research in Tumor Immunology, Osaka University Graduate School of Medicine Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine
  • Kanazawa Takayuki
    Shionogi Co., Ltd.
  • Yamamoto Yoko
    Department of Clinical Research in Tumor Immunology, Osaka University Graduate School of Medicine Department of General Thoracic Surgery, Osaka University Graduate School of Medicine
  • Goto Kumiko
    Shionogi Co., Ltd. Department of Clinical Research in Tumor Immunology, Osaka University Graduate School of Medicine
  • Kawashima Atsunari
    Department of Urology, Osaka University Graduate School of Medicine
  • Morimoto-Okazawa Akiko
    Department of Clinical Research in Tumor Immunology, Osaka University Graduate School of Medicine
  • Funaki Soichiro
    Department of General Thoracic Surgery, Osaka University Graduate School of Medicine
  • Shintani Yasushi
    Department of General Thoracic Surgery, Osaka University Graduate School of Medicine
  • Kumanogoh Atsushi
    Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine
  • Wada Hisashi
    Department of Clinical Research in Tumor Immunology, Osaka University Graduate School of Medicine

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<p>Immune checkpoint inhibitors (ICIs) exert beneficial effects in non-small cell lung cancer (NSCLC) patients. However, ICIs are only advantageous for a limited population of NSCLC patients. Therefore to enhance their effects, combination therapies with ICIs have been developed. To identify preferable chemotherapy to combine with ICIs against lung cancer, we examined immunological effects of docetaxel compared with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). We found no difference in peripheral lymphocyte counts and ratio of their subpopulations in lung cancer patients before and after both treatments. On the other hand, plasma levels of high-mobility group box 1 (HMGB1), a damage-associated molecular pattern (DAMP) protein, showed significant increase after docetaxel treatment. Furthermore, we investigated effects of HMGB1 on tumor-infiltrating immune cells obtained from surgically resected tumor tissue from NSCLC patients. When the tumor infiltrating cells were stimulated with HMGB1, CD11c+ cells showed increased expression of activation markers. These findings imply that docetaxel could be involved in anti-tumor immunity via HMGB1. Therefore docetaxel might be a candidate for combination treatment with ICIs.</p>

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