2021 AACR: Longitudinal Exome-Scale Liquid Biopsy Monitoring of Evolving Therapeutic Resistance Mechanisms in Head and Neck Squamous Cell Carcinoma Patients Receiving Anti-PD-1 Therapy

Typical liquid biopsy panels capture a relatively small number of variants, and likely under-represent the heterogeneity of resistance in late-stage cancers. To address the challenges associated with identifying multiple concurrent heterogeneous resistance mechanisms in individual patients, we evaluated longitudinal whole exome sequencing of cell free DNA (cfDNA) and solid tumor biopsies from head and neck squamous cell carcinoma (HNSCC) patients that received anti-PD1 therapy. Using this approach, we identified evolving variant and pathway-level resistance mechanisms in cfDNA as a complement to tumor biopsy-derived information, and identified differences in putative neoantigens.

Cohort

Pre- and post-intervention matched tumor, normal and plasma samples were obtained from a cohort of 15 patients with HNSCC. Following baseline sample collection, all patients received a single dose of nivolumab. The primary tumor was then resected, approximately one month later when possible, or a second biopsy was collected where resection was impractical.

Solid Tumor

Paired tumor and normal samples were profiled using ImmunoID NeXT, an augmented exome/ transcriptome platform and analysis pipeline which produces comprehensive tumor mutation information, gene expression profiling, neoantigen characterization including our composite neoantigen burden score NEOPSTM, HLA typing and allele-specific LOH, TCR repertoire profiling, and tumor microenvironment profiling as outlined in the plot below.

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