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Poster display session

1946 - The role of PD-L1 in a high-grade invasive human oral squamous cell carcinoma microenvironment.

Date

11 Sep 2017

Session

Poster display session

Topics

Translational Research;  Head and Neck Cancers

Presenters

MARIKO HIRAI

Citation

Annals of Oncology (2017) 28 (suppl_5): v595-v604. 10.1093/annonc/mdx391

Authors

M. HIRAI, H. kitahara, Y. Kobayashi, S. Kawashiri, H. Nakamura

Author affiliations

  • Oral And Maxillofacial Surgery, Kanazawa University Graduate School of Medical Science, 920-8641 - Kanazawa/JP
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Resources

Abstract 1946

Background

Blockade of the programmed-death 1 receptor (PD-1)/programmed-death ligand (PD-L1) pathway efficiently reduces tumour growth and improves survival. Durable tumour regression with blockade of the PD-1/PD-L1 checkpoint has been demonstrated in recent clinical studies. Oral squamous cell carcinoma (OSCC) is highly immunosuppressive, and PD-L1 expression has been proposed as a potential mechanism responsible for this phenotype. Despite the fact that anti-PD-1 treatment can produce durable responses, such therapy appears to benefit only a subset of patients. Thus, it is important to understand the mechanisms underlying the regulation of PD-L1 expression in the OSCC microenvironment.

Methods

The subjects were patients with primary OSCC who underwent surgical resection at the Kanazawa University Hospital between 1998 and 2008. And, three human oral squamous cell carcinoma cell lines established from tumor biopsies with different grade of invasive abilities were used: OSC-20, OSC-19 and TSU.

Results

We showed that PD-L1 expression in high-grade invasive OSCC cell lines was lower than that in a low-grade invasive OSCC line and found a close correlation between PD-L1 expression and the epithelial-mesenchymal transition (EMT). PD-L1 expression was upregulated in macrophages and dendritic cells (DCs) in high-grade invasive human OSCC tissues or co-cultured with mesenchymal-phenotype OSCC cells in vitro. TLR4-inhibitory peptide successfully suppressed PD-L1 upregulation on macrophages and DCs co-cultured with mesenchymal-phenotype OSCC cells, suggesting that some EMT-induced tumour antigen is critical for PD-L1 induction on tumour-associated macrophages and DCs.

Conclusions

Further studies are necessary to explore the impact of EMT on the tumour immune microenvironment and to identify potential biomarkers for selecting patients who might preferentially benefit from PD-1/PD-L1 blockade or immunotherapies more broadly.

Clinical trial identification

Legal entity responsible for the study

Kanazawa University

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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