Purpose: Programmed death-1 (PD-1) inhibitors are approved for the treatment of patients with recurrent and metastatic squamous cell carcinoma of the head and neck (SCCHN). Ongoing and planned randomized phase 3 trials are testing the benefit of combining PD-1/programmed death-ligand 1 (PD-L1) inhibitors with chemoradiation for patients with locoregionally confined SCCHN. Few studies have investigated relationships among potential predictive pathologic biomarkers such as PD-L1, PD-L2, and PD-1 in this population and associations between these markers and clinical characteristics. Methods and Materials: We retrospectively reviewed records and pathology from 81 patients with locoregional oropharynx SCCHN treated with curative intent. Samples were analyzed for PD-L1, PD-L2, PD-1, CD8, and CD56 expression using immunohistochemistry. Human papilloma virus (HPV) status was determined by p16-immunohistochemistry and confirmed by in situ hybridization or polymerase chain reaction−based HPV typing. Correlations between HPV status, clinical features, and recurrence status with immune markers in both tumor and tumor-associated stroma were determined. Hazard ratios were estimated via Cox proportional hazards model. Results: Tumor PD-L1 expression was inversely associated with age (P =.01) and the highest levels of expression (>30% of tumor cells) were observed in HPV-associated tumors. There was a correlation between tumor and stromal PD-L1 expression (P = <.0001). PD-1 and CD8 expression within tumor deposits was associated with HPV status (P = 0.003 and P =.008, respectively) and decreased local recurrence (P =.001 and P <.001, respectively). In addition to the association between tumor and stromal PD-1 (P <.0001), PD-1 was also correlated with tumor PD-L1 expression (P <.001). CD56+ natural killer cell infiltrates correlated with PD-L1 expression. Conclusions: In patients with untreated oropharyngeal SCCHN, HPV-associated tumors displayed the highest levels of PD-L1 expression and PD-1+ and CD8+ immune cells. Locally recurrent tumors had lower levels of PD-L1, PD-1, and CD-8 positivity. Whereas almost all SCCHN tumors had CD56+ infiltrating natural killer cells, most tumors didn't have PD-L2 expression. These associations may help predict which patients may benefit most from immunotherapeutic approaches.
|Original language||English (US)|
|Number of pages||9|
|Journal||International Journal of Radiation Oncology Biology Physics|
|State||Published - Sep 1 2018|
ASJC Scopus subject areas
- Radiology Nuclear Medicine and imaging
- Cancer Research