Objectives: Nivolumab has recently been shown in the phase III clinical trial CheckMate-141 to have superior survival rates compared to the current standard of care chemotherapy for recurrent or metastatic platinum-resistant head and neck squamous cell carcinoma (HNSCC). Nivolumab targets the immune inhibitory receptor programmed cell death 1 (PD-1). Programmed cell death ligand 1 (PD-L1) genomics have been poorly characterized in the context of HNSCC, including expression levels of PD-L1 in individual tumors as well as related up or down-regulated genes that might function as co-targets.
Study design: Data mining of The Cancer Genome Atlas (TCGA).
Methods: 530 patients with HNSCC were pulled from the TCGA using cBioPortal. Primary tumor site data was available in 279 of the samples (52.6%), of which oral cavity was the most common site (61.6%) followed by larynx (25.8%). Other PD-1-sensitive tumors were analyzed to compare PD-L1 expression in HNSCC relative to other tumors including bladder, renal cell carcinoma, melanoma, and lung carcinomas.
Results: A significant fraction of HNSCC tumors have genetic alterations in PD-L1 (6.2%). HNSCC has the highest PD-L1 expression of all of the tumor types examined, with a median 60-fold increase. Several important genes were identified in this study including Caspase 7, ZFYVE9, and Plg-R(KT) that have a strong relationship with alterations in PD-L1.
Conclusion: In light of the role of PD-1 and PD-L1 as key immunotherapy targets in HNSCC, several potential co-targets identified in this study warrant further investigation. Further, while the number of genetic alterations were small in head and neck carcinomas, alterations in PD-L1 expression were highly significant.
Level of evidence: NA.
Keywords: Immunotherapy; head and neck cancer; programmed death ligand.