TY - JOUR
T1 - Evaluating the PD-1 Axis and Immune Effector Cell Infiltration in Oropharyngeal Squamous Cell Carcinoma
AU - Schoenfeld, Jonathan D.
AU - Gjini, Evisa
AU - Rodig, Scott J.
AU - Tishler, Roy B.
AU - Rawal, Bhupendra
AU - Catalano, Paul J.
AU - Uppaluri, Ravindra
AU - Haddad, Robert I.
AU - Hanna, Glenn J.
AU - Chau, Nicole G.
AU - Rabinowits, Guilherme
AU - Lorch, Jochen
AU - Jo, Vickie Y.
AU - Krane, Jeffrey F.
AU - Goguen, Laura A.
AU - Annino, Donald J.
AU - Abdelrahman, Sara
AU - Lipschitz, Mikel
AU - Margalit, Danielle N.
N1 - Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2018/9/1
Y1 - 2018/9/1
N2 - 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.
AB - 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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U2 - 10.1016/j.ijrobp.2018.05.002
DO - 10.1016/j.ijrobp.2018.05.002
M3 - Article
C2 - 29960819
AN - SCOPUS:85049053103
SN - 0360-3016
VL - 102
SP - 137
EP - 145
JO - International Journal of Radiation Oncology Biology Physics
JF - International Journal of Radiation Oncology Biology Physics
IS - 1
ER -
