2021 SITC: Tumor-informed liquid biopsy monitoring of evolving therapeutic resistance mechanisms in head and neck squamous cell carcinoma patients receiving anti-PD-1 therapy

Background

Typical liquid biopsy panels offer a limited understanding of tumor biology, potentially under-representing the heterogeneity of resistance in late-stage cancers. Here, diminished scope can result in undetected, therapeutically-relevant biomarkers which respond dynamically to treatment, as well as potentially missed resistance mechanisms and pathway-level events. To address the challenges associated with identifying multiple concurrent heterogeneous resistance mechanisms in individual patients, we evaluated longitudinal exome-scale tumor-informed cell-free DNA (cfDNA) data from head and neck squamous cell carcinoma (HNSCC) patients receiving anti-PD1 therapy.

Methods

Cohort: Pre- and post-intervention matched tumor, normal and plasma samples were obtained from a cohort of 15 patients with stage II-IV HNSCC. After 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 the ImmunoID NeXT Platform®, 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 NEOPS™, HLA typing and allele-specific loss of heterozygosity (HLA LOH), TCR repertoire profiling, and tumor microenvironment profiling as outlined in the plot below.

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