title: Pan-Cancer Immunogenomic Perspective on the Tumor Microenvironment Based on PD-L1 and CD8 T-Cell Infiltration.
abstract: There is currently no reliable biomarker to predict who would benefit from anti-PD-1/PD-L1 inhibitors. We comprehensively analyzed the immunogenomic properties in The Cancer Genome Atlas (TCGA) according to the classification of tumor into four groups based on PD-L1 status and tumor-infiltrating lymphocyte recruitment (TIL), a combination that has been suggested to be a theoretically reliable biomarker of anti-PD-1/PD-L1 inhibitors.
  
  
  
  The RNA expression levels of PD-L1 and CD8A in the samples in the pan-cancer database of TCGA (N = 9,677) were analyzed. Based on their median values, the samples were classified into four tumor microenvironment immune types (TMIT). The mutational profiles, PD-L1 amplification, and viral association of the samples were compared according to the four TMITs.
  
  
  
  The proportions of TMIT I, defined by high PD-L1 and CD8A expression, were high in lung adenocarcinoma (67.1%) and kidney clear cell carcinoma (64.8%) among solid cancers. The number of somatic mutations and the proportion of microsatellite instable-high tumor in TMIT I were significantly higher than those in other TMITs, respectively (P < 0.001). PD-L1 amplification and oncogenic virus infection were significantly associated with TMIT I, respectively (P < 0.001). A multivariate analysis confirmed that the number of somatic mutations, PD-L1 amplification, and Epstein-Barr virus/human papillomavirus infection were independently associated with TMIT I.
  
  
  
  TMIT I is associated with a high mutational burden, PD-L1 amplification, and oncogenic viral infection. This integrative analysis highlights the importance of the assessment of both PD-L1 expression and TIL recruitment to predict responders to immune checkpoint inhibitors. Clin Cancer Res; 22(9); 2261-70. ©2016 AACRSee related commentary by Schalper et al., p. 2102.
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Chan-Young
authors.initials: CY
authors.lastname: Ock
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea. Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea. bhumsuk@snu.ac.kr.
authors.forename: Bhumsuk
authors.initials: B
authors.lastname: Keam
authors.affiliation: Department of Pathology, Seoul National University Hospital Seoul, Korea.
authors.forename: Sehui
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Ju-Seog
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Miso
authors.initials: M
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea. Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Tae Min
authors.initials: TM
authors.lastname: Kim
authors.affiliation: Department of Pathology, Seoul National University Hospital Seoul, Korea.
authors.forename: Yoon Kyung
authors.initials: YK
authors.lastname: Jeon
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea. Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Dong-Wan
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Department of Pathology, Seoul National University Hospital Seoul, Korea.
authors.forename: Doo Hyun
authors.initials: DH
authors.lastname: Chung
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea. Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Dae Seog
authors.initials: DS
authors.lastname: Heo
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology / Q000821:virology; D000077192:Adenocarcinoma of Lung; D060890:B7-H1 Antigen / Q000276:immunology*; D016827:CD8 Antigens / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000821:virology; D020031:Epstein-Barr Virus Infections / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D008175:Lung Neoplasms / Q000276:immunology / Q000821:virology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000821:virology; D009858:Oncogenic Viruses / Q000276:immunology; D030361:Papillomavirus Infections / Q000276:immunology; D059016:Tumor Microenvironment / Q000276:immunology*
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human; D016827:CD8 Antigens