PMID- 25046660 OWN - NLM STAT- MEDLINE DCOM- 20150226 LR - 20220310 IS - 1097-0215 (Electronic) IS - 0020-7136 (Linking) VI - 136 IP - 5 DP - 2015 Mar 1 TI - Human natural killer cells promote cross-presentation of tumor cell-derived antigens by dendritic cells. PG - 1085-94 LID - 10.1002/ijc.29087 [doi] AB - Dendritic cells (DCs) cross-present antigen (Ag) to initiate T-cell immunity against most infections and tumors. Natural killer (NK) cells are innate cytolytic lymphocytes that have emerged as key modulators of multiple DC functions. Here, we show that human NK cells promote cross-presentation of tumor cell-derived Ag by DC leading to Ag-specific CD8(+) T-cell activation. Surprisingly, cytotoxic function of NK cells was not required. Instead, we highlight a critical and nonredundant role for IFN-gamma and TNF-alpha production by NK cells to enhance cross-presentation by DC using two different Ag models. Importantly, we observed that NK cells promote cell-associated Ag cross-presentation selectively by monocytes-derived DC (Mo-DC) and CD34-derived CD11b(neg) CD141(high) DC subsets but not by myeloid CD11b(+) DC. Moreover, we demonstrate that triggering NK cell activation by monoclonal antibodies (mAbs)-coated tumor cells leads to efficient DC cross-presentation, supporting the concept that NK cells can contribute to therapeutic mAbs efficiency by inducing downstream adaptive immunity. Taken together, our findings point toward a novel role of human NK cells bridging innate and adaptive immunity through selective induction of cell-associated Ag cross-presentation by CD141(high) DC, a process that could be exploited to better harness Ag-specific cellular immunity in immunotherapy. CI - (c) 2014 UICC. FAU - Deauvieau, Florence AU - Deauvieau F AD - Inserm UMR-S1052, Centre de Recherche en Cancerologie de Lyon, Lyon, France; CNRS UMR5286, Centre de Recherche en Cancerologie de Lyon, Lyon, France; UNIV UMR1052, Centre de Recherche en Cancerologie de Lyon, Lyon, France; Universite de Lyon, Lyon, France; Centre Leon Berard, Lyon, France. FAU - Ollion, Vincent AU - Ollion V FAU - Doffin, Anne-Claire AU - Doffin AC FAU - Achard, Carole AU - Achard C FAU - Fonteneau, Jean-Francois AU - Fonteneau JF FAU - Verronese, Estelle AU - Verronese E FAU - Durand, Isabelle AU - Durand I FAU - Ghittoni, Raffaella AU - Ghittoni R FAU - Marvel, Jacqueline AU - Marvel J FAU - Dezutter-Dambuyant, Colette AU - Dezutter-Dambuyant C FAU - Walzer, Thierry AU - Walzer T FAU - Vie, Henri AU - Vie H FAU - Perrot, Ivan AU - Perrot I FAU - Goutagny, Nadege AU - Goutagny N FAU - Caux, Christophe AU - Caux C FAU - Valladeau-Guilemond, Jenny AU - Valladeau-Guilemond J LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140806 PL - United States TA - Int J Cancer JT - International journal of cancer JID - 0042124 RN - 0 (Antigens, Neoplasm) SB - IM MH - Antibody-Dependent Cell Cytotoxicity MH - Antigen Presentation/*immunology MH - Antigens, Neoplasm/*immunology MH - Cross-Priming/*immunology MH - Dendritic Cells/*immunology/pathology MH - Humans MH - Immunity, Cellular/*immunology MH - Killer Cells, Natural/*immunology/pathology MH - Neoplasms/*immunology/pathology MH - Tumor Cells, Cultured OTO - NOTNLM OT - NK cell OT - cross-presentation OT - dendritic cell OT - mAb therapy EDAT- 2014/07/22 06:00 MHDA- 2015/02/27 06:00 CRDT- 2014/07/22 06:00 PHST- 2013/10/08 00:00 [received] PHST- 2014/06/18 00:00 [accepted] PHST- 2014/07/22 06:00 [entrez] PHST- 2014/07/22 06:00 [pubmed] PHST- 2015/02/27 06:00 [medline] AID - 10.1002/ijc.29087 [doi] PST - ppublish SO - Int J Cancer. 2015 Mar 1;136(5):1085-94. doi: 10.1002/ijc.29087. Epub 2014 Aug 6.