Abstract
Purpose
We aimed to investigate the prognostic value of multiple immune cell markers including programmed death-ligand 1 (PD-L1) and poliovirus receptor (PVR) in head and neck squamous cell carcinoma (HNSCC) using archival tumor tissues
Methods
Patients diagnosed with HNSCC who have undergone surgical resection in 2005–2012 were included. Correlations between PVR and PD-L1 expression and patient characteristics were analyzed by analysis of variance. The Kaplan–Meier method and log-rank test were used to estimate survival. P values < 0.05 were considered statistically significant.
Results
In total, 375 primary tumor tissues were analyzed using immunohistochemistry. High PVR expression was associated with a poor prognosis in terms of overall survival (OS) and recurrence-free survival (RFS), and tumors with high PVR expression were associated with a short OS. PD-L1 tumor expression did not have a prognostic impact on survival. Univariate analysis revealed that OS and RFS were affected by age and p16 and PVR expression; multivariate analysis revealed that age and p16 and PVR expression were the most important determinants of RFS.
Conclusion
PVR overexpression is a poor prognostic factor in patients with HNSCC and co-targeting PVR and PD-L1 may be a promising therapeutic option that needs further investigation.
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Funding
This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean Government (MSIT) (NRF-2017M3A9E9072669, 2017M3A9E8029717, NRF-2019M3A9B6065231(sc) to H.R.K. and 2018R1A2A1A05076997, 2017R1A5A1014560) and by a grant from the National R&D Program for Cancer Control, Ministry of Health and Welfare, Republic of Korea (HA16C0015, HA16C0015020019).
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Conceptualization, formal analysis, funding acquisition, and writing: SM LDHH, SH, SOY, and HRK. All the authors reviewed and edited the manuscript.
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432_2021_3531_MOESM1_ESM.pptx
Supplementary file1 Online Resource 1. PD-L1 expression on immunohistochemistry. (a) Negative PD-L1 expression (b) Positive PD-L1 expression is defined as PD-L1 expression on ≥5% of tumor cells. Online Resource 2. PVR expression on immunohistochemistry (a) Normal skeletal muscle cells reveal strong cytoplasmic expression of PVR (thick arrows). Other stromal cells do not express PVR. Almost all of the tumor cells (in dotted area) reveal PVR expression in the cytoplasmic membrane with intensity score 1 (b) Part of normal endothelial cells reveal weak to moderate cytoplasmic expression of PVR (thin arrows). Other stromal cells do not express PVR. Almost all tumor cells (in dotted area) do not express PVR, and less than 5% of tumor cells expressed PVR in the cytoplasmic membrane. Online Resource 3 Kaplan-Meier curves of overall survival (OS) and recurrence-free survival (RFS) according to PD-L1 expression of tumor stratified to 2 groups (PD-L1 negative vs. positive). (a) OS compared between PD-L1 expression of negative vs. positive patients (P=0.307) (b) RFS compared between PD-L1 expression of negative vs. positive patients (P=0.046). Online Resource 6. A pie chart depicting the distribution of four groups. 1) PD-L1high/PVRlow, 2) PD-L1low/PVRlow, 3) PD-L1high/PVRhigh, and 4) PD-L1low/PVRhigh. Online Resource 11. Kaplan-Meier curves comparing overall survival of among IChigh and IClow group among patients with PVRlow expression. (PPTX 2854 KB)
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Lim, S.M., Hong, M.H., Ha, SJ. et al. Overexpression of poliovirus receptor is associated with poor prognosis in head and neck squamous cell carcinoma patients. J Cancer Res Clin Oncol 147, 2741–2750 (2021). https://doi.org/10.1007/s00432-021-03531-8
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DOI: https://doi.org/10.1007/s00432-021-03531-8