PMID- 18942710 OWN - NLM STAT- MEDLINE DCOM- 20090115 LR - 20210105 IS - 1097-0215 (Electronic) IS - 0020-7136 (Linking) VI - 124 IP - 2 DP - 2009 Jan 15 TI - Reciprocal activating interaction between 6-sulfo LacNAc+ dendritic cells and NK cells. PG - 358-66 LID - 10.1002/ijc.23962 [doi] AB - Dendritic cells (DCs) display an extraordinary capacity to induce T-cell responses providing the opportunity of DC-based cancer vaccination strategies. Additional findings indicate that DCs may also play a crucial role for the activation of natural killer (NK) cells, which are important effectors in innate antitumor immunity. However, studies investigating the interaction between native human DCs and NK cells are limited. Recently, we defined 6-sulfo LacNAc (slan) DCs as a major subpopulation of myeloid human blood DCs, which represent principal producers of the proinflammatory cytokines tumor necrosis factor-alpha and interleukin (IL)-12. Functional data revealed that slanDCs efficiently induce neoantigen-specific CD4+ T cells and activate tumor-reactive cytotoxic T cells. When evaluating the crosstalk between slanDCs and NK cells in this study, we found that lipopolysaccharide (LPS)-activated slanDCs efficiently enhance NK cell CD69 expression and interferon (IFN)-gamma secretion. NK cell-mediated tumor-directed cytotoxicity was significantly improved by slanDCs. NK cell activation induced by slanDCs was critically dependent on IL-12. When investigating the impact of NK cells on the immunostimulatory capacity of slanDCs, we observed that they promote DC maturation. In addition, NK cells strongly enhanced the secretion of immunomodulatory IL-12 and reduced the release of immunosuppressive IL-10 by slanDCs. IFN-gamma and cell-to-cell contact contributed to these effects. Furthermore, data revealed that DC-NK cell crosstalk improves slanDC-mediated differentiation of naive CD4+ T lymphocytes into IFN-gamma-producing Th1 cells. In conclusion, we demonstrate a reciprocal activating interaction between slanDCs and NK cells, which may play a pivotal role in the regulation of antitumor immunity. CI - Copyright (c) 2008 Wiley-Liss, Inc. FAU - Wehner, Rebekka AU - Wehner R AD - Institute of Immunology, Department of Medicine I, Medical Faculty, Technical University of Dresden, Dresden, Germany. FAU - Lobel, Barbel AU - Lobel B FAU - Bornhauser, Martin AU - Bornhauser M FAU - Schakel, Knut AU - Schakel K FAU - Cartellieri, Marc AU - Cartellieri M FAU - Bachmann, Michael AU - Bachmann M FAU - Rieber, Ernst Peter AU - Rieber EP FAU - Schmitz, Marc AU - Schmitz M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Int J Cancer JT - International journal of cancer JID - 0042124 RN - 0 (6-sulfo-LacNac) RN - 0 (Amino Sugars) RN - 0 (Antigens, CD) RN - 0 (Antigens, Differentiation, T-Lymphocyte) RN - 0 (CD69 antigen) RN - 0 (Cytokines) RN - 0 (Lectins, C-Type) RN - 0 (Lipopolysaccharides) RN - 0 (Tumor Necrosis Factor-alpha) RN - 130068-27-8 (Interleukin-10) RN - 187348-17-0 (Interleukin-12) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Amino Sugars/*metabolism MH - Antigens, CD/biosynthesis MH - Antigens, Differentiation, T-Lymphocyte/biosynthesis MH - Cytokines/metabolism MH - Dendritic Cells/cytology/*metabolism MH - Humans MH - Interferon-gamma/metabolism MH - Interleukin-10/metabolism MH - Interleukin-12/metabolism MH - K562 Cells MH - Killer Cells, Natural/*metabolism MH - Lectins, C-Type MH - Leukocytes, Mononuclear/cytology MH - Lipopolysaccharides/metabolism MH - Lymphocyte Activation MH - Models, Biological MH - Tumor Necrosis Factor-alpha/metabolism EDAT- 2008/10/24 09:00 MHDA- 2009/01/16 09:00 CRDT- 2008/10/24 09:00 PHST- 2008/10/24 09:00 [entrez] PHST- 2008/10/24 09:00 [pubmed] PHST- 2009/01/16 09:00 [medline] AID - 10.1002/ijc.23962 [doi] PST - ppublish SO - Int J Cancer. 2009 Jan 15;124(2):358-66. doi: 10.1002/ijc.23962.