Abstract 955P
Background
Immune checkpoint inhibitors targeting programmed cell death protein 1 (PD-1) improve survival in a subset of patients with head and neck squamous cell carcinoma (HNSCC). However, there are many patients who do not achieve clinical benefit with these agents, despite positive expression of the of the programmed death-ligand 1 (PD-L1). Here, we aimed to investigate the immune resistance mechanism in head and neck squamous cell carcinoma.
Methods
The genomic data and clinical data of the discovery cohort was obtained from The Cancer Genome Atlas (TCGA). The clinical data for the validation cohort in HNSCC treated with immunotherapy was retrospectively collected from Chinese patients. Whole exome sequencing was performed on tissue from patients with HNSCC in a College of American Pathologists-certified and Clinical Laboratory Improvement Amendments-accredited lab.
Results
Activation of WNT signaling was inferred from somatic mutations or somatic copy number alterations in WNT signaling elements, including CTNNB1, APC, AXIN1, AXIN2, CSNK1A,WNT1,WNT2,WNT3,WNT4,WNT6, WNT7,WNT8, WNT9, WNT10, WNT16, GSK3, SMAD3, SMAD4 and BCL9L. Two cohorts were analysed in this study, the discovery cohort from the TCGA, and the validation cohort from Chinese patients with HNSCC. The frequency of WNT pathway alterations in the TCGA cohort was 33.3%, and this represented mutually exclusive molecular subsets. In the TCGA cohort, activating alterations in WNT signaling were associated with shorter median PFS (2.8 vs 3.4 months) and OS (11.1 vs 20.7 months).
Conclusions
Mutations predicted to activate the WNT signaling pathway were associated with innate resistance to immune checkpoint blockade in head and neck squamous cell carcinoma.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
F. Gong, Y. Bai: Full/Part-time employment: 3D Medicines Inc. All other authors have declared no conflicts of interest.