title: An Immunogram for the Cancer-Immunity Cycle: Towards Personalized Immunotherapy of Lung Cancer.
abstract: The interaction of immune cells and cancer cells shapes the immunosuppressive tumor microenvironment. For successful cancer immunotherapy, comprehensive knowledge of antitumor immunity as a dynamic spatiotemporal process is required for each individual patient. To this end, we developed an immunogram for the cancer-immunity cycle by using next-generation sequencing.
  
  
  
  Whole exome sequencing and RNA sequencing were performed in 20 patients with NSCLC (12 with adenocarcinoma, seven with squamous cell carcinoma, and one with large cell neuroendocrine carcinoma). Mutated neoantigens and cancer germline antigens expressed in the tumor were assessed for predicted binding to patients' human leukocyte antigen molecules. The expression of genes related to cancer immunity was assessed and normalized to construct a radar chart composed of eight axes reflecting seven steps in the cancer-immunity cycle.
  
  
  
  Three immunogram patterns were observed in patients with lung cancer: T-cell-rich, T-cell-poor, and intermediate. The T-cell-rich pattern was characterized by gene signatures of abundant T cells, regulatory T cells, myeloid-derived suppressor cells, checkpoint molecules, and immune-inhibitory molecules in the tumor, suggesting the presence of antitumor immunity dampened by an immunosuppressive microenvironment. The T-cell-poor phenotype reflected lack of antitumor immunity, inadequate dendritic cell activation, and insufficient antigen presentation in the tumor. Immunograms for both the patients with adenocarcinoma and the patients with nonadenocarcinoma tumors included both T-cell-rich and T-cell-poor phenotypes, suggesting that histologic type does not necessarily reflect the cancer immunity status of the tumor.
  
  
  
  The patient-specific landscape of the tumor microenvironment can be appreciated by using immunograms as integrated biomarkers, which may thus become a valuable resource for optimal personalized immunotherapy.
authors.affiliation: Department of Thoracic Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Karasaki
authors.affiliation: Department of Thoracic Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nagayama
authors.affiliation: Department of Thoracic Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Kuwano
authors.affiliation: Department of Thoracic Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Jun-Ichi
authors.initials: JI
authors.lastname: Nitadori
authors.affiliation: Department of Thoracic Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Sato
authors.affiliation: Department of Thoracic Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Anraku
authors.affiliation: Department of Immunotherapeutics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Medinet Co. Ltd., Yokohama, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Hosoi
authors.affiliation: Department of Immunotherapeutics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Matsushita
authors.affiliation: Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Morishita
authors.affiliation: Department of Biostatistics, School of Public Health, The University of Tokyo, Tokyo, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Kashiwabara
authors.affiliation: Department of Technology Development, Kazusa DNA Research Institute, Kisarazu, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Takazawa
authors.affiliation: Department of Technology Development, Kazusa DNA Research Institute, Kisarazu, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Ohara
authors.affiliation: Department of Immunotherapeutics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. Electronic address: kakimi@m.u-tokyo.ac.jp.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kakimi
authors.affiliation: Department of Thoracic Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Nakajima
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000276:immunology*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000276:immunology; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000276:immunology* / Q000628:therapy*; D005260:Female; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics / Q000276:immunology*; D007167:Immunotherapy; D008175:Lung Neoplasms / Q000235:genetics / Q000276:immunology* / Q000628:therapy*; D008213:Lymphocyte Activation / Q000235:genetics; D016131:Lymphocyte Subsets; D016246:Lymphocytes, Tumor-Infiltrating; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D057285:Precision Medicine; D012334:RNA, Neoplasm / Q000032:analysis; D017423:Sequence Analysis, RNA; D013601:T-Lymphocytes / Q000276:immunology; D059016:Tumor Microenvironment / Q000235:genetics / Q000276:immunology; D000073359:Exome Sequencing
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D006680:HLA Antigens; D012334:RNA, Neoplasm
keywords: Cancer-immunity cycle; Immunogram; Lung cancer; Neoantigen; Transcriptome