Immune subtypes and neoantigen-related immune evasion in advanced colorectal cancer
Toshitaka Sugawara,
Fuyuki Miya,
Toshiaki Ishikawa,
Artem Lysenko,
Jo Nishino,
Takashi Kamatani,
Akira Takemoto,
Keith A. Boroevich,
Kazuhiro Kakimi,
Yusuke Kinugasa,
Minoru Tanabe,
Tatsuhiko Tsunoda
Affiliations
Toshitaka Sugawara
Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan
Fuyuki Miya
Department of Medical Science Mathematics, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan; Laboratory for Medical Science Mathematics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan; Laboratory for Medical Science Mathematics, Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo 113-0033, Japan; Center for Medical Genetics, Keio University School of Medicine, Tokyo 160-8582, Japan; Corresponding author
Toshiaki Ishikawa
Department of Specialized Surgeries, Tokyo Medical and Dental University (TMDU), Graduate School of Medicine and Dentistry, Bunkyo-ku, Tokyo 113-8510, Japan
Artem Lysenko
Laboratory for Medical Science Mathematics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan
Jo Nishino
Division of Bioinformatics, Research Institute, National Cancer Center Japan, Tokyo 104-0045, Japan
Takashi Kamatani
Department of Medical Science Mathematics, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan; Laboratory for Medical Science Mathematics, Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo 113-0033, Japan; Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan
Akira Takemoto
Bioresource Research Center, Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan
Keith A. Boroevich
Laboratory for Medical Science Mathematics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan
Kazuhiro Kakimi
Department of Immunotherapeutics, The University of Tokyo Hospital, Tokyo 113-8655, Japan
Yusuke Kinugasa
Department of Gastrointestinal Surgery, Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan
Minoru Tanabe
Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan
Tatsuhiko Tsunoda
Department of Medical Science Mathematics, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan; Laboratory for Medical Science Mathematics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan; Laboratory for Medical Science Mathematics, Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo 113-0033, Japan; CREST, JST, Tokyo 113-0033, Japan; Corresponding author
Summary: Elimination of cancerous cells by the immune system is an important mechanism of protection from cancer, however, its effectiveness can be reduced owing to development of resistance and evasion. To understand the systemic immune response in advanced untreated primary colorectal cancer, we analyze immune subtypes and immune evasion via neoantigen-related mechanisms. We identify a distinctive cancer subtype characterized by immune evasion and very poor overall survival. This subtype has less clonal highly expressed neoantigens and high chromosomal instability, resulting in adaptive immune resistance mediated by the immune checkpoint molecules and neoantigen presentation disorders. We also observe that neoantigen depletion caused by immunoediting and high clonal neoantigen load are correlated with a good overall survival. Our results indicate that the status of the tumor microenvironment and neoantigen composition are promising new prognostic biomarkers with potential relevance for treatment plan decisions in advanced CRC.
