Abstract 5138: The PD-1/PD-L1 axis and clinical outcomes in head and neck squamous cell carcinomas

Abstract

Abstract Although novel therapeutic agents targeting PD-L1 and PD-1 have emerged, our understanding of the complex interaction between the tumor microenvironment and this checkpoint receptor-ligand axis remains incomplete. PD-L1 protein expression has been demonstrated by immunohistochemistry in several solid tumors including head and neck squamous cell carcinomas (HNSCC). However, the prognostic significance of PD-L1 overexpression in HNSCC remains inconclusive. Furthermore, the interaction between human papillomavirus (HPV) positive tumors, PD-L1 on tumor cells and PD-1 on immune cells has yet to be demonstrated in an architecturally intact tumor environment. Here we demonstrate PD-L1 expression in a large cohort of mixed HPV+ and HPV-, surgically treated HNSCC using immunohistochemistry. Our findings confirm that more HPV+ tumors express PD-L1 compared with HPV- tumors (72% compared with 44%). Clinically, this correlates with improved overall and disease-free survival in in patients with HPV+ PD-L1+ tumors compared with HPV- PD-L1- tumors. By examining the intact tumor, we visualized distinct patterns of PD-L1 staining, either peripherally, at the tumor front or non-peripherally. Tumors with a peripheral staining pattern showed a trend towards decreased overall and disease-free survival, compared to those with a non-peripheral pattern of staining. By double staining PD-L1 and PD-1, we analyzed the co-expression of the ligand on tumor cells and its receptor on neighboring immune cells. Interestingly, patients whose tumors displayed co-localization of PD-1 and PD-L1 showed a trend towards improved disease-free survival compared to tumors where there was no co-localization of PD-1 and PD-L1. In conclusion, out data suggest that the presence of PD-L1 and PD-1 alone may not be sufficient to guide clinical treatment rather; careful examination of the intact tumor microenvironment may inform more targeted therapy. Citation Format: Sumita Trivedi, Raja R. Seethala, Robert L. Ferris. The PD-1/PD-L1 axis and clinical outcomes in head and neck squamous cell carcinomas. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5138.