Jonathan D Schoenfeld1, Evisa Gjini2, Scott J Rodig2, Roy B Tishler3, Bhupendra Rawal4, Paul J Catalano4, Ravindra Uppaluri5, Robert I Haddad6, Glenn J Hanna6, Nicole G Chau6, Guilherme Rabinowits6, Jochen Lorch6, Vickie Y Jo7, Jeffrey F Krane7, Laura A Goguen5, Donald J Annino5, Sara Abdelrahman2, Mikel Lipschitz2, Danielle N Margalit3. 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.
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:TumorPD-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 tumorPD-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.
Authors: Rachel A Woolaver; Xiaoguang Wang; Alexandra L Krinsky; Brittany C Waschke; Samantha M Y Chen; Vince Popolizio; Andrew G Nicklawsky; Dexiang Gao; Zhangguo Chen; Antonio Jimeno; Xiao-Jing Wang; Jing Hong Wang Journal: J Immunother Cancer Date: 2021-01 Impact factor: 13.751