title: Characteristics and clinical impacts of the immune environments in colorectal and renal cell carcinoma lung metastases: influence of tumor origin.
abstract: OBJECTIVE
  If immune cells are involved in tumor surveillance and have a prognostic impact in most primary tumors, little is known about their significance in metastases. Because patients' survival is heterogeneous, even at metastatic stages, we hypothesized that immune cells may be involved in the control of metastases. We therefore characterized the tumor immune microenvironment and its prognostic value in colorectal and renal cell carcinoma (RCC) metastases, and compared it to primary tumors.
  
  
  METHODS
  We analyzed by immunohistochemistry (n = 192) and qPCR (n = 32) the immune environments of colorectal carcinoma and RCC lung metastases.
  
  
  RESULTS
  Metastases from colorectal carcinoma and RCC have different immune infiltrates. Higher densities of DC-LAMP(+) mature dendritic cells (P < 0.0001) and lower densities of NKp46(+) NK cells (P < 0.0001) were observed in colorectal carcinoma as compared to RCC metastases, whereas densities of T cells were similar. High densities of CD8(+) and DC-LAMP(+) cells correlated with longer overall survival (OS) in colorectal carcinoma (P = 0.008) and shorter OS in RCC (P < 0.0001). High NK-cell densities were associated with improved survival in RCC (P = 0.002) but not in colorectal carcinoma. Densities of immune cells correlated significantly from primary to relapsing metastases for the same patient. A TH1 orientation was found in colorectal carcinoma metastases, whereas a heterogeneous immune gene expression was found in RCC metastases.
  
  
  CONCLUSIONS
  Our results show a major prognostic value of the immune pattern (CD8(+)/DC-LAMP(+) cell densities) in colorectal carcinoma and RCC, reproducible from primary to metastatic tumors, although with opposite clinical impacts, and highlight the role of the tumor cell in shaping its immune environment.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), U872, Centre de Recherche des Cordeliers, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Remark
authors.forename: Marco
authors.initials: M
authors.lastname: Alifano
authors.forename: Isabelle
authors.initials: I
authors.lastname: Cremer
authors.forename: Audrey
authors.initials: A
authors.lastname: Lupo
authors.forename: Marie-Caroline
authors.initials: MC
authors.lastname: Dieu-Nosjean
authors.forename: Marc
authors.initials: M
authors.lastname: Riquet
authors.forename: Lucile
authors.initials: L
authors.lastname: Crozet
authors.forename: Hanane
authors.initials: H
authors.lastname: Ouakrim
authors.forename: Jeremy
authors.initials: J
authors.lastname: Goc
authors.forename: Aurélie
authors.initials: A
authors.lastname: Cazes
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Fléjou
authors.forename: Laure
authors.initials: L
authors.lastname: Gibault
authors.forename: Virginie
authors.initials: V
authors.lastname: Verkarre
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Régnard
authors.forename: Olivier-Nicolas
authors.initials: ON
authors.lastname: Pagès
authors.forename: Stéphane
authors.initials: S
authors.lastname: Oudard
authors.forename: Bernhard
authors.initials: B
authors.lastname: Mlecnik
authors.forename: Catherine
authors.initials: C
authors.lastname: Sautès-Fridman
authors.forename: Wolf-Herman
authors.initials: WH
authors.lastname: Fridman
authors.forename: Diane
authors.initials: D
authors.lastname: Damotte
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000276:immunology; D002292:Carcinoma, Renal Cell / Q000276:immunology* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000473:pathology; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000276:immunology* / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology; D059016:Tumor Microenvironment / Q000276:immunology*
chemical_list: D014408:Biomarkers, Tumor