Regulation of programmed-death ligand in the human head and neck squamous cell carcinoma microenvironment is mediated through matrix metalloproteinase-mediated proteolytic cleavage

• MIYAZAWA（HIRA） Mayuko

  Department of Oral and Maxillofacial Surgery, Kanazawa University Graduate School of Medical Science

• NAKAMURA Hiroyuki

  Department of Oral and Maxillofacial Surgery, Kanazawa University Graduate School of Medical Science

• HIRAI Mariko

  Department of Oral and Maxillofacial Surgery, Kanazawa University Graduate School of Medical Science

• KOBAYASHI Yutaka

  Department of Oral and Maxillofacial Surgery, Kanazawa University Graduate School of Medical Science

• KITAHARA Hiroko

  Department of Oral and Maxillofacial Surgery, Kanazawa University Graduate School of Medical Science

• KAWASHIRI Shuichi

  Department of Oral and Maxillofacial Surgery, Kanazawa University Graduate School of Medical Science

Bibliographic Information

Other Title

• 翻訳論文：ヒト頭頸部扁平上皮癌の微小環境における マトリックスメタロプロテナーゼを介したPD-1 リガンドの調節機構

Abstract

Recurrent and/or metastatic head and neck squamous cell carcinoma（R/M HNSCC） is a devastating malignancy with a poor prognosis. According to recent clinical studies, tumor growth can be effectively reduced and survival can be improved by blocking the programmed death receptor 1（PD-1） pathway. However, anti-PD-1 treatment is beneficial only for certain patients. Therefore, the mechanisms controlling PD-L1 expression warrant further investigation in order to provide a better understanding of the efficacy of predicting and optimizing anti-PD-1 therapy, alone or in combination. In this study, PD-L1 protein extracted from the cell membrane was found to be downregulated in OSC-20 cells compared with OSC-19 cells, despite a higher PD-L1 expression in the total cell lysate of the OSC-20 compared with the OSC-19 cells. Several matrix metalloproteinases（MMPs） were found to be upregulated in HNSCC; in particular, MMP-7 and -13 were upregulated in the OSC-20 compared with the OSC-19 cells. Purified PD-L1 was degraded by recombinant MMP-13 and -7. The expression of PD-L1 was significantly restored by a specific inhibitor of MMP-13, which suggested the involvement of MMP-13 in the shedding/cleavage of PD-L1 in the OSC-20 cells. Among the anti-cancer drugs conventionally used in the treatment of patients with HNSCC, paclitaxel increased MMP-13 expression in R/M HNSCC cells（HOC313 cells）. These results suggest that the shedding/cleavage of PD-L1 by MMP-13 is one of the mechanisms behind the protective effect against invasion and metastasis. Thus, MMP-13 has potential value as a marker predictive of the decreased efficacy of anti-PD-1 therapy.

Journal

• Journal of The Japanese Stomatological Society

  Journal of The Japanese Stomatological Society 67 (4), 260-270, 2018

  Japanese Stomatological Society

Keywords

• recurrent and/or metastatic head and neck squamous cell carcinoma
• programmed death receptor 1
• programmed death‑ligand-1
• matrix metalloproteinase
• tumor microenvironment

Details

• CRID: 1390001288121937536
• NII Article ID: 130007595071
• DOI: 10.11277/stomatology.67.260
• ISSN: 21850461
• ISSN: 00290297
• Text Lang: ja
• Data Source:
  • JaLC
  • CiNii Articles
• Abstract License Flag: Disallowed