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Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

2738 - Matrix metalloproteinase-mediated regulation of programmed-death ligand in the human head and neck squamous cell carcinoma microenvironment

Date

21 Oct 2018

Session

Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

Presenters

MARIKO HIRAI

Citation

Annals of Oncology (2018) 29 (suppl_8): viii1-viii13. 10.1093/annonc/mdy268

Authors

M. HIRAI1, Y. Kobayashi2, M.H. Miyazawa2, H. kitahara3, S. Kawashiri2, H. Nakamura2

Author affiliations

  • 1 Oral And Maxillofacial Surgery, Tonami General Hospital, 9391395 - tonami/JP
  • 2 Oral And Maxillofacial Surgery, Kanazawa University Hospital, 9208641 - Kanazawa/JP
  • 3 Oral And Maxillofacial Surgery, Kanazawa University Hospital, 920-8641 - Kanazawa/JP
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Resources

Abstract 2738

Background

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, tumour growth can be effectively reduced and survival can be improved by blocking the programmed death receptor 1 (PD-1)/programmed death-ligand 1 (PD-L1) 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 predicting efficacy of and optimising anti-PD-1 therapy, alone or in combination.

Methods

MMP-mediated regulation of PD-L1 expression was examined in three human HNSCC cell lines (OSC-20, OSC-19 and HOC313). Enzymatic activity of MMP against PD-L1 was evaluated in vitro using purified recombinant proteins or MMP synthetic inhibitors.

Results

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 (CL82198), 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) co-cultured without/with dendritic cells (DCs).

Conclusions

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. In addition, paclitaxel is a particularly promising candidate for combination therapy in R/M HNSCC with anti-PD-1 therapy.

Clinical trial identification

Legal entity responsible for the study

Graduate School of Medical Science, Kanazawa University.

Funding

Has not received any funding.

Editorial Acknowledgement

Disclosure

All authors have declared no conflicts of interest.

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