PMID- 21325295 OWN - NLM STAT- MEDLINE DCOM- 20110815 LR - 20210103 IS - 1557-3265 (Electronic) IS - 1078-0432 (Linking) VI - 17 IP - 4 DP - 2011 Feb 15 TI - Natural killer cells are scarce in colorectal carcinoma tissue despite high levels of chemokines and cytokines. PG - 678-89 LID - 10.1158/1078-0432.CCR-10-2173 [doi] AB - PURPOSE: 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. EXPERIMENTAL DESIGN: 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. CI - (c)2011 AACR. FAU - Halama, Niels AU - Halama N AD - Medical Oncology, National Center for Tumor Diseases, University Heidelberg, Germany. FAU - Braun, Monika AU - Braun M FAU - Kahlert, Christoph AU - Kahlert C FAU - Spille, Anna AU - Spille A FAU - Quack, Christian AU - Quack C FAU - Rahbari, Nuh AU - Rahbari N FAU - Koch, Moritz AU - Koch M FAU - Weitz, Jurgen AU - Weitz J FAU - Kloor, Matthias AU - Kloor M FAU - Zoernig, Inka AU - Zoernig I FAU - Schirmacher, Peter AU - Schirmacher P FAU - Brand, Karsten AU - Brand K FAU - Grabe, Niels AU - Grabe N FAU - Falk, Christine S AU - Falk CS LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Clin Cancer Res JT - Clinical cancer research : an official journal of the American Association for Cancer Research JID - 9502500 RN - 0 (CD56 Antigen) RN - 0 (Cell Adhesion Molecules) RN - 0 (Chemokines) RN - 0 (Cytokines) RN - 0 (NCAM1 protein, human) RN - 0 (NCR1 protein, human) RN - 0 (Natural Cytotoxicity Triggering Receptor 1) RN - 0 (Selectins) SB - IM MH - Adult MH - Aged MH - CD56 Antigen/metabolism MH - Cell Adhesion Molecules/metabolism MH - Cell Movement MH - Chemokines/*metabolism MH - Colorectal Neoplasms/metabolism/*pathology MH - Cytokines/*metabolism MH - Female MH - Humans MH - Intestinal Mucosa/pathology MH - Killer Cells, Natural/*metabolism MH - Liver/pathology MH - Liver Neoplasms/metabolism/pathology/secondary MH - Male MH - Middle Aged MH - Natural Cytotoxicity Triggering Receptor 1/metabolism MH - Selectins/metabolism MH - T-Lymphocytes/metabolism EDAT- 2011/02/18 06:00 MHDA- 2011/08/16 06:00 CRDT- 2011/02/18 06:00 PHST- 2011/02/18 06:00 [entrez] PHST- 2011/02/18 06:00 [pubmed] PHST- 2011/08/16 06:00 [medline] AID - 17/4/678 [pii] AID - 10.1158/1078-0432.CCR-10-2173 [doi] PST - ppublish SO - Clin Cancer Res. 2011 Feb 15;17(4):678-89. doi: 10.1158/1078-0432.CCR-10-2173.