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Int J Radiat Oncol Biol Phys. 2018 Sep 1;102(1):137-145. doi: 10.1016/j.ijrobp.2018.05.002. Epub 2018 Jun 29.

Evaluating the PD-1 Axis and Immune Effector Cell Infiltration in Oropharyngeal Squamous Cell Carcinoma.

Author information

1
Department of Radiation Oncology, Brigham & Women's Hospital/Dana-Farber Cancer Institute, Boston, Massachusetts. Electronic address: jonathan_schoenfeld@dfci.harvard.edu.
2
Department of Pathology, Brigham & Women's Hospital, Boston, Massachusetts; Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
3
Department of Radiation Oncology, Brigham & Women's Hospital/Dana-Farber Cancer Institute, Boston, Massachusetts.
4
Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.
5
Division of Otolaryngology, Department of Surgery, Brigham & Women's Hospital/Dana-Farber Cancer Institute, Boston, Massachusetts.
6
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
7
Department of Pathology, Brigham & Women's Hospital, Boston, Massachusetts.

Abstract

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.

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