Expression of PD-L1, PD-L2, and inflammatory gene expression profile in locally advanced head and neck squamous cell carcinoma

Abstract

Background: The tumor immune microenvironment in cancer treatment response and resistance is of increasing interest. This retrospective study characterized and investigated programmed death-ligand 1 (PD-L1), PD-L2, and the immune gene expression signature and their association with clinical outcomes in locoregionally advanced head and neck squamous cell carcinoma (LA HNSCC).

Patients and methods: PD-L1 and PD-L2 expression on tumor and immune-infiltrating cells (positivity defined as combined positive score or immunohistochemistry proportion score >1) and T-cell-inflamed gene expression profile (Tcell_infGEP) were evaluated in patients with LA HNSCC treated in South Korea from 2000 to 2015. Correlations among the three biomarkers and their associations with overall survival and recurrence-free survival were assessed.

Results: Among 366 patients, 38.8% had human papillomavirus-positive disease. PD-L1-positive, PD-L2-positive, and high Tcell_infGEP (≤-0.162) status were observed in 83.6%, 85.4%, and 73.2% of patients, respectively; 4.1% were posttreatment samples. Correlation between PD-L1 and PD-L2 scores was moderate (r_Spearman = 0.50), and each biomarker was slightly less correlated with Tcell_infGEP (0.41-0.45). PD-L1 expression and high Tcell_infGEP status were associated with human papillomavirus positivity. Higher levels of all biomarkers were observed in oral cavity and oropharyngeal cancers compared with other HNSCC sites. In a multivariable analysis that simultaneously adjusted for all three biomarkers, only high Tcell_infGEP was significantly associated with longer overall survival (adjusted hazard ratio, 0.57; 95% confidence interval 0.33-0.98) and recurrence-free survival (adjusted hazard ratio, 0.41; 95% confidence interval 0.23-0.74).

Conclusion: High Tcell_infGEP status, but not PD-L1 or PD-L2 expression, was independently associated with longer survival in patients with LA HNSCC. Results may have implications for evaluating therapies targeting programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) in HNSCC.

Keywords: PD-L1; PD-L2; gene expression profile; head and neck squamous cell carcinoma; programmed cell death protein 1.

Figure 1

Correlation between (A) PD-L1 and PD-L2, (B) PD-L1 and Tcell_infGEP, and (C) PD-L2 and Tcell_infGEP scores. Both PD-L1 and PD-L2 scores have been square-root transformed to minimize outsized influence of large values. PD-L1, programmed death-ligand 1; PD-L2, programmed death-ligand 2; Tcell_infGEP, T-cell- inflamed gene expression profile.

Figure 2

Kaplan–Meier curves of (A-C) overall survival and (D-F) recurrence-free survival, by singular biomarker status. Biomarkers were assessed singularly in separate models. aHR, adjusted hazard ratio; cHR, crude hazard ratio; CI, confidence interval; PD-L1, programmed death-ligand 1; PD-L2, programmed death-ligand 2; RFS, recurrence-free survival; Tcell_infGEP, T-cell-inflamed gene expression profile.