title: Immune cell infiltration as an indicator of the immune microenvironment of pancreatic cancer.
abstract: BACKGROUND
  The host immune reaction is represented by immune/inflammatory cell infiltrates. Here we systematically analysed tumour-infiltrating immune/inflammatory cells in pancreatic ductal carcinoma (PDC) and evaluated their clinicopathological impact.
  
  
  METHODS
  Using immunohistochemistry, we examined tumour-infiltrating CD68(+) pan-macrophages, HLA-DR(+)CD68(+) M1 macrophages (M1), CD163(+) or CD204(+) M2 macrophages (M2), CD66b(+) neutrophils (Neu), CD4(+) T cells (CD4(+)T), CD8(+) T cells (CD8(+)T), and FOXP3(+)CD4(+) regulatory T cells (Treg) in 212 cases of PDC, and conducted correlation and survival analyses using the Kaplan-Meier method and Cox proportional hazards model.
  
  
  RESULTS
  Higher levels of tumour-infiltrating pan-macrophages, M2, Neu, or the ratio of Tregs to CD4(+)T (%Treg) were significantly associated with shorter survival, whereas higher levels of tumour-infiltrating CD4(+)T, CD8(+)T, or the ratio of M1 to pan-macrophages (%M1) were significantly associated with longer survival. Survival analysis of pairs of these variables revealed that some of the resulting patient groups had exclusively longer survival. We then connected the apparently related factors, and two significant variables emerged: tumour-infiltrating CD4(+)T(high)/CD8(+)T(high)/%Treg(low) and tumour-infiltrating %M1(high)/M2(low). Multivariate survival analysis revealed that these variables were significantly correlated with longer survival and had a higher hazard ratio.
  
  
  CONCLUSIONS
  Tumour-infiltrating CD4(+)T(high)/CD8(+)T(high)/%Treg(low) and %M1(high)/M2(low) are independent prognosticators useful for evaluating the immune microenvironment of PDC.
authors: Division of Molecular Pathology, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
authors: Y
authors: Y
authors: Ino
authors: R
authors: R
authors: Yamazaki-Itoh
authors: K
authors: K
authors: Shimada
authors: M
authors: M
authors: Iwasaki
authors: T
authors: T
authors: Kosuge
authors: Y
authors: Y
authors: Kanai
authors: N
authors: N
authors: Hiraoka
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D016019:Survival Analysis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D059016:Tumor Microenvironment
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