T cells can inhibit tumor growth and progression by recognizing major histocompatibility complex class I (MHC-I) -bound peptides derived from antigens that are mutated, inappropriately expressed, or overexpressed in the tumor cells (vs. healthy cells). There are many mechanisms by which tumors can avoid recognition or destruction by the immune system. Among them is HLA loss of heterozygosity (LOH), which occurs when a maternal or paternal HLA haplotype is lost, and can result in reduced tumor-specific antigen presentation. HLA-LOH has been associated impaired response to checkpoint blockade immunotherapy. Although HLA LOH is emerging as a key biomarker for response to immunotherapy, few tools exist to detect HLA LOH. Here, we describe DASH (Deletion of Allele-Specific HLAs), an algorithm to detect HLA LOH from exome sequencing data, and present a three-pronged validation approach to assess its performance.
The ImmunoID NeXT Platform® provides joint tumor genomics and immune profiling from a paired tumor and healthy normal sample. Through augmented coverage of the HLA locus, ImmunoID NeXT also provides the data to accurately type HLA alleles, detect somatic mutations and probe copy number deletions in this highly polymorphic region.
