Head and Neck Cancer

PV QA 2 - Poster Viewing Q&A 2

MO_34_2780 - Prognostic Role of PD-1/PD-L1 Expression in Patients With Head And Neck Cancer and Its Correlation With HPV/p16

Monday, October 22
10:45 AM - 12:15 PM
Location: Innovation Hub, Exhibit Hall 3

Prognostic Role of PD-1/PD-L1 Expression in Patients With Head And Neck Cancer and Its Correlation With HPV/p16
X. Lv, Q. Qiao, and G. Li; Department of Radiation Oncology, the First Hospital of China Medical University, Shenyang, China

Purpose/Objective(s): The expression of programmed cell death protein 1 (PD1)/programmed cell death-ligand 1 (PD-L1) in tumor cells contributes to a mechanism that allows cancer cells to escape from immune surveillance.The aim of the present study was to investigate the prognostic value of PD-1/PD-L1 expression in patients with head and neck cancer in The Cancer Genome Atlas(TCGA) dataset who were treated with radiotherapy.

Materials/Methods: We analyzed the PD-1/PD-L1 expression levels of patients with head and neck cancer in the TCGA dataset. According to the identified gene signature related to radiosensitivity, 289 patients were selected and divided into two clusters using a consensus clustering algorithm. The two clusters were designated as radiosensitive (RS) and radioresistant (RR). Patients were also stratified as PD-L1-high or PD-L1-low on the basis of CD274 mRNA expression level as a surrogate of PD-L1 and PDCD1 mRNA as a surrogate of PD-1.

Results: Patients assigned to the RS group had a better overall survival (OS) (hazard ratio [HR], 0.6089; 95% confidence interval [CI], 0.4045–0.9167;p= 0.0026) and recurrence-free survival (RFS) (HR, 0.6647; 95% CI, 0.4155–1.063;p = 0.0121) compared with patients in the RR group by univariate analysis only when treated with radiotherapy. The human papilloma virus (HPV)/p16–positive group had significantly high PD-1 expression (p<0.0001).PD-L1 expression was significantly higher in the RS group (p=0.0005) than in the RR group. In the PD-L1-high patients, the RR group was associated with worse OS (HR, 3.68; 95% CI, 1.426-9.493;p = 0.007) than the RS group in multivariate analysis. It has been reported that the level of PD-L1 expression is positively related to the level of tumor-infiltrating lymphocytes (TILs).It has been revealed that TILs level is an independent prognostic factor for improved progression-free survival. Thus, we speculated that the PD-L1-high group had more TILs, which could be more sensitive to radiotherapy. In the patients who were treated with radiotherapy, the PD-1-highgroup was associated with better RFS (HR, 0.4892; 95% CI, 0.2357 to 1.015;p = 0.023). This is probably due to functionally anergic CD4-positive TILs, which are an independent prognostic factor for decreased RFS,leading to the expression of PD-1.Within the RR group, the PD-L1-high group had lower OS (HR,2.196; 95% CI,1.081–4.46, p = 0.0108) than the PD-L1-low group. This phenomenon could be explained by the activation of epidermal growth factor receptor (EGFR) in radiation-resistant tumors. EGFR inhibits the activation of CD8-positive T cells and causes tumor immune escape through the up regulation of PD-L1.

Conclusion: PD-1 expression is significantly high in HPV/p16-positive patients. Also, PD-1/PD-L1 expression is an important factor for prediction of the clinical prognosis in patients with head and neck cancer treated with radiotherapy, and patients with a radioresistant gene signature will benefit from radiotherapy combined with anti-PD-1/PD-L1 therapy.

Author Disclosure: X. Lv: None. Q. Qiao: None.

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