title: Role of tumor-infiltrating CD11b+ antigen-presenting cells in the progression of gastric cancer.
abstract: BACKGROUND
  Tumor-infiltrating antigen-presenting cells (APCs), involving tumor-associated macrophages and tumor-infiltrating dendritic cells, play an important role in tumor immunity and immune escape. The aim of this study was to determine whether tumor infiltrating CD11b(+) APCs may affect tumor progression and clinical outcome.
  
  
  METHODS
  The immunohistochemical analysis was used to evaluate the expression of CD11b, FOXP3, and CD8 in 214 gastric cancer tissues. Concentrations of immunosuppressive cytokines in medium conditioned by gastric cancer cells were measured by enzyme-linked immunosorbent assay. Effects of addition of tumor-conditioned media on CD11c(+) cells were examined by flow cytometry.
  
  
  RESULTS
  Almost all tumor-infiltrating CD11b(+) cell expressed CD11c and was considered to be APCs. High CD11b(+) cell infiltration was significantly correlated with huge tumor, positive venous invasion, lymph node metastasis, and tumor, node, metastasis stage. Patients with high CD11b(+) cell infiltration had a poorer surgical outcome than those with low CD11b infiltration. Multivariate analysis revealed that CD11b(+) cell infiltration was one of the independent prognostic factors. Tumor-conditioned medium obtained from several gastric cancer cell lines contained immunosuppressive cytokines, transforming growth factor-beta, interleukin-10, and vascular endothelial growth factor. The addition of tumor-conditioned medium decreased the expression of major histocompatibility complex-II and increased the expression of CD11b and programmed death ligand 2 on CD11c(+) APCs. Infiltration of CD11b(+) cells significantly correlate with the degree of FOXP3(+) cell infiltration but not with CD8(+) cell infiltration.
  
  
  CONCLUSIONS
  Tumor-infiltrating CD11b(+) APCs affected local tumor cell-immune cell interactions and correlated to the poor prognosis of the patients with gastric cancer.
authors.affiliation: Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Okita
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Tanaka
authors.forename: Masaichi
authors.initials: M
authors.lastname: Ohira
authors.forename: Kazuya
authors.initials: K
authors.lastname: Muguruma
authors.forename: Naoshi
authors.initials: N
authors.lastname: Kubo
authors.forename: Mao
authors.initials: M
authors.lastname: Watanabe
authors.forename: Wakaba
authors.initials: W
authors.lastname: Fukushima
authors.forename: Kosei
authors.initials: K
authors.lastname: Hirakawa
mesh_terms: D000938:Antigen-Presenting Cells / Q000502:physiology*; D039481:CD11b Antigen / Q000032:analysis*; D018450:Disease Progression; D005260:Female; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000502:physiology; D008297:Male; D008875:Middle Aged; D013274:Stomach Neoplasms / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D015996:Survival Rate
chemical_list: D039481:CD11b Antigen; C509295:ITGAM protein, human
keywords: Dendritic cell; Gastric cancer; Prognosis