Exome scale liquid biopsy characterization of putative neoantigens and genomic biomarkers pre- and post anti-PD-1 therapy in squamous cell carcinoma of the head and neck.

Abstract

6557 Background: The reduced scope, and number of genes profiled by typical liquid biopsy panels can result in missed biomarkers including neoantigens, which may change with treatment, as well as potentially undetected resistance mechanisms and pathways beyond the scope of targets typically captured by panels. To address these limitations, we used a whole-exome scale liquid biopsy monitoring platform, NeXT Liquid Biopsy, to analyze head and neck squamous cell carcinoma (HNSCC) patients that have received anti-PD1 therapy. Presently, we sought to (1) monitor neoantigen changes in cfDNA as a complement to tumor biopsy-derived neoantigens, (2) compare the impact of tumor escape mechanisms, including HLA-LOH, on neoantigens identified in tissue and cfDNA and (3) to identify novel biological signatures that combine information from both solid tumor and liquid biopsies. Methods: Pre- and post-intervention matched normal, tumor and plasma samples were collected from a cohort of 12 patients with HNSCC. Following baseline sample collection all patients received a single dose of nivolumab, followed by resection approximately one month later when feasible, or a second biopsy where resection was impractical. Solid tumor and matched normal samples were profiled using ImmunoID NeXT, an augmented exome/transcriptome platform and analysis pipeline. Exome-scale somatic variants were identified in cfDNA from plasma samples using the NeXT Liquid Biopsy platform. Data from these two platforms were compared with corresponding clinical findings. Results: Concordant somatic events were detected between plasma and tumor at pre- and post-treatment timepoints. Neoantigens predicted to arise from these somatic events were reduced in solid tumor post-treatment, but increased in cfDNA, when compared to pre-treatment timepoints. HLA LOH was identified in a number of subjects, likely resulting in reduced neoepitope presentation in those cases. Immune cell infiltration increased in the tumor following treatment, with no changes to the CD8+/Treg cell ratio, suggesting consistent immunoregulation. Conclusions: Exome-wide neoantigen burden was reliably predicted from cfDNA, providing additional insight complementing data from solid tumor. Analyzing HLA LOH, and neoantigen burden from both solid and liquid biopsies together over the course of treatment creates a more comprehensive profile of therapeutic response and resistance mechanisms in HNSCC patients missed with typical liquid biopsy panels.