title: Natural killer cells are scarce in colorectal carcinoma tissue despite high levels of chemokines and cytokines.
abstract: OBJECTIVE
  Tumor infiltrating T lymphocytes in colorectal cancer (CRC) have prognostic impact, but the role of natural killer (NK) cells in CRC tissue is unclear. The contribution of intratumoral cytokines and chemokines in shaping the composition of the inflammatory lymphocytic infiltrate is also unclear.
  
  
  METHODS
  In this study, localization and densities of NK and T cells within primary CRC, CRC liver metastases, adenomas, and normal tissues were analyzed on whole tissue sections from 112 patients. In a subset of these patients, the most important 50 cytokines and chemokines were quantified in paired serum, primary CRC and adjacent mucosa samples and in CRC liver metastases and correlated with NK and T-cell infiltration, respectively.
  
  
  RESULTS
  The various compartments displayed characteristic differences like significantly higher chemokine concentrations in CRC tissue. Most importantly, despite high local chemokine levels, NK cells were generally scarce within CRC tumor tissues, independent of human leukocyte antigen (HLA) class I expression. Adjacent normal mucosa contained normal levels of NK cells. In contrast, corresponding T-cell numbers varied substantially and were positively correlated with higher chemokine levels.
  
  
  CONCLUSIONS
  Our findings indicate a distinct regulation of NK cells versus T cells in the CRC tumor microenvironment. NK-cell migration into CRC tumor tissue is obviously impaired early during tumor development by mechanisms that do not affect T-cell infiltration.
authors.affiliation: Medical Oncology, National Center for Tumor Diseases, University Heidelberg, Germany.
authors.forename: Niels
authors.initials: N
authors.lastname: Halama
authors.forename: Monika
authors.initials: M
authors.lastname: Braun
authors.forename: Christoph
authors.initials: C
authors.lastname: Kahlert
authors.forename: Anna
authors.initials: A
authors.lastname: Spille
authors.forename: Christian
authors.initials: C
authors.lastname: Quack
authors.forename: Nuh
authors.initials: N
authors.lastname: Rahbari
authors.forename: Moritz
authors.initials: M
authors.lastname: Koch
authors.forename: Jürgen
authors.initials: J
authors.lastname: Weitz
authors.forename: Matthias
authors.initials: M
authors.lastname: Kloor
authors.forename: Inka
authors.initials: I
authors.lastname: Zoernig
authors.forename: Peter
authors.initials: P
authors.lastname: Schirmacher
authors.forename: Karsten
authors.initials: K
authors.lastname: Brand
authors.forename: Niels
authors.initials: N
authors.lastname: Grabe
authors.forename: Christine S
authors.initials: CS
authors.lastname: Falk
mesh_terms: D000328:Adult; D000368:Aged; D019002:CD56 Antigen / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002465:Cell Movement; D018925:Chemokines / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology; D007694:Killer Cells, Natural / Q000378:metabolism*; D008099:Liver / Q000473:pathology; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology / Q000556:secondary; D008297:Male; D008875:Middle Aged; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000378:metabolism; D019087:Selectins / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism
chemical_list: D019002:CD56 Antigen; D015815:Cell Adhesion Molecules; D018925:Chemokines; D016207:Cytokines; C522918:NCAM1 protein, human; C112260:NCR1 protein, human; D055627:Natural Cytotoxicity Triggering Receptor 1; D019087:Selectins