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

宮澤（平） 真優子, 中村 博幸, 平井 真理子, 小林 泰, 北原 寛子, 川尻 秀一

doi:10.11277/stomatology.67.260

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.

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

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