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

Shinichi Mizuno, Rui Yamaguchi, Takanori Hasegawa, View ORCID ProfileShuto Hayashi, Masashi Fujita, Fan Zhang, Youngil Koh, Su-Yeon Lee, Sung-Soo Yoon, View ORCID ProfileEigo 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: https://doi.org/10.1101/285338
Shinichi Mizuno
1Center for Advanced Medical Innovation, Kyushu University, Fukuoka, Japan
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Rui Yamaguchi
2Human Genome Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
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Takanori Hasegawa
3Health Intelligence Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
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Shuto Hayashi
2Human Genome Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
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Masashi Fujita
4Laboratory for Cancer Genomics, RIKEN Center for Integrative Medical Sciences, Tokyo, Japan
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Fan Zhang
5BIOPIC and College of Life Sciences, Academy for Advanced Interdisciplinary Studies, Beijing Advanced Innovation Centre for Genomics, Peking University, Beijing, China
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Youngil Koh
6Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
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Su-Yeon Lee
7Samsung SDS, Seoul, Korea
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Sung-Soo Yoon
6Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
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Eigo Shimizu
2Human Genome Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
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  • ORCID record for Eigo Shimizu
Mitsuhiro Komura
2Human Genome Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
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Akihiro Fujimoto
4Laboratory for Cancer Genomics, RIKEN Center for Integrative Medical Sciences, Tokyo, Japan
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Momoko Nagai
8National Cancer Research Center, Tokyo, Japan
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Mamoru Kato
8National Cancer Research Center, Tokyo, Japan
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Han Liang
9Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
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Satoru Miyano
2Human Genome Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
3Health Intelligence Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
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Zemin Zhang
5BIOPIC and College of Life Sciences, Academy for Advanced Interdisciplinary Studies, Beijing Advanced Innovation Centre for Genomics, Peking University, Beijing, China
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  • For correspondence: imoto@ims.u-tokyo.ac.jp
Hidewaki Nakagawa
4Laboratory for Cancer Genomics, RIKEN Center for Integrative Medical Sciences, Tokyo, Japan
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  • For correspondence: imoto@ims.u-tokyo.ac.jp
Seiya Imoto
3Health Intelligence Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
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  • For correspondence: imoto@ims.u-tokyo.ac.jp
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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 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.

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Posted April 12, 2019.
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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
bioRxiv 285338; doi: https://doi.org/10.1101/285338
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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
bioRxiv 285338; doi: https://doi.org/10.1101/285338

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