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

Shinichi Mizuno; Rui Yamaguchi; Takanori Hasegawa; Shuto Hayashi; Masashi Fujita; Fan Zhang; Youngil Koh; Su‐Yeon Lee; Sung‐Soo Yoon; Eigo Shimizu; Mitsuhiro Komura; Akihiro Fujimoto; Momoko Nagai; Mamoru Kato; Han Liang; Satoru Miyano; Zemin Zhang; Hidewaki Nakagawa; Seiya Imoto; on behalf of the PCAWG Mitochondrial Genome and Immunogenomics Working Group and The PCAWG Network

doi:10.1101/285338

GenomicsbioRxivApr 12, 2019

Preprint

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

Shinichi Mizuno iD, Rui Yamaguchi iD, Takanori Hasegawa iD, Shuto Hayashi iD, Masashi Fujita iD, Fan Zhang iD, Youngil Koh iD, Su‐Yeon Lee iD, Sung‐Soo Yoon iD, Eigo Shimizu iD, Mitsuhiro Komura, Akihiro Fujimoto iD, Momoko Nagai, Mamoru Kato iD, Han Liang iD, Satoru Miyano iD, Zemin Zhang iD, Hidewaki Nakagawa iD, Seiya Imoto iD, on behalf of the PCAWG Mitochondrial Genome and Immunogenomics Working Group and The PCAWG Network

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 genome-immune 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 PanCancer Analysis of Whole Genomes (PCAWG) project with respect to key immuno-genomic 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.

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