2020 AACR: Sensitive HLA loss of heterozygosity detection reveals allele-specific neoantigen expansion as resistance

Loss of heterozygosity (LOH) in the HLA locus is increasingly being recognized as an important mechanism of immune escape and a proposed biomarker for immunotherapy response. Neoantigens that bind to a deleted HLA allele will no longer be presented to the immune system, potentially allowing subclones with these deletions to escape immune surveillance. Despite interest in the field, few methods exist to detect HLA LOH, and their sensitivity is not well understood. Moreover, the mechanistic impact of HLA LOH in response to immune checkpoint inhibitors (ICI) remains unexplored.

The ImmunoID NeXT Platform® provides joint tumor genomics and immune profiling from a single tumor/normal sample. Through augmenting coverage of the HLA locus, the ImmunoID NeXT Platform also provides the data to accurately type HLA alleles, detect somatic mutations and probe copy number deletions in this highly polymorphic region.

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