Immuno-genomic PanCancer Landscape Reveals Diverse Immune Escape Mechanisms and Immuno-Editing Histories

Abstract

Immune reactions in the tumor micro-environment are one of the cancer hallmarks and emerging immune therapies have been proven effective in many types of cancer. To investigate cancer genomeimmune interactions and the role of immuno-editing or immune escape mechanisms in cancer development, we analyzed 2,834 whole genomes and RNA-seq datasets across 31 distinct tumor types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) project with respect to key immunogenomic aspects. We show that selective copy number changes in immune-related genes could contribute to immune escape. Furthermore, we developed an index of the immuno-editing history of each tumor sample based on the information of mutations in exonic regions and pseudogenes. Our immuno-genomic analyses of pan-cancer analyses have the potential to identify a subset of tumors with immunogenicity and diverse background or intrinsic pathways associated with their immune status and immuno-editing history.All rights reserved. No reuse allowed without permission.(which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.

ALPHLARD-NT: Bayesian Method for Human Leukocyte Antigen Genotyping and Mutation Calling through Simultaneous Analysis of Normal and Tumor Whole-Genome Sequence Data

“…This figure demonstrates the high sensitivity of ALPHLARD-NT (88 mutations) compared with POLYSOLVER (60 mutations) and EBCall (80 mutations), which is especially remarkable for insertions. ALPHLARD-NT detected seven insertions at the beginning of exon 4 of HLA class I genes, which is a known hotspot of indels (Mizuno et al, 2018), whereas POLYSOLVER and EBCall identified no and three insertions at this hotspot, respectively. ALPHLARD-NT also identified 12 deletions at the same position.…”

Neoantimon: a multifunctional R package for identification of tumor-specific neoantigens

“…Furthermore, substantial evidence indicates that tumor-specific peptides that result from such variations can bind to a major histocompatibility complex (MHC) molecule and be presented to antitumor T cells on the surface of a tumor cell. Identification of such tumor-specific peptides, termed neoantigens, has been receiving increasing attention because of its numerous potential applications in cancer immunotherapy ( Carreno et al , 2015 ; Matsushita et al , 2012 ; Mizuno et al , 2018 ).…”

“…It can automatically construct mutant peptides from vcf files or mutant RNA sequences and calculate their binding capability to the corresponding HLAs with some information for filtering. This tool has been used in the Mitochondrial Genome and Immunogenomics Working Group in the PanCancer Analysis of Whole Genomes (PCAWG) project ( Mizuno et al , 2018 ).…”

A multifunctional R package for identification of tumor-specific neoantigens

“…Recent technological advances in massively parallel sequencing have enabled 2 identification of genetic variants, e.g., single nucleotide variants (SNVs) and insertions 3 or deletions (Indels), in individual cancer patients. Furthermore, substantial evidence 4 indicates that tumor-specific peptides that result from such variations can bind to a 5 major histocompatibility complex (MHC) molecule and be presented to antitumor 6 T-cells on the surface of a tumor cell. Identification of such tumor-specific peptides, 7 termed neoantigens, has been receiving increasing attention because of its numerous 8 potential applications in cancer immunotherapy.…”

“…Beyond 69 previously developed platforms, it can cover specific cases and include additional 70 information for filtering. The package, documentation, and sample analysis are 71 available at http://github/hase62/Neoantimon, and an analysis result in PCAWG 72 project is also available[5]. An overview of the input and output file information of the package.…”