title: Prolonged antitumor NK cell reactivity elicited by CXCL10-expressing dendritic cells licensed by CD40L+ CD4+ memory T cells.
abstract: Immunotherapy using dendritic cells (DCs) has the potential to activate both T cells and NK cells. We previously demonstrated the long-lasting antitumor responses by NK cells following immunization with bone marrow-derived DCs. In the current study, we demonstrate that long-term antitumor NK responses require endogenous DCs and a subset of effector memory CD4(+) T (CD4(+) T(EM)) cells. One month after DC immunization, injection of a tumor into DC-immunized mice leads to an increase in the expression of CXCL10 by endogenous DCs, thus directing NK cells into the white pulp where the endogenous DCs bridged CD4(+) T(EM) cells and NK cells. In this interaction, CD4(+) T(EM) cells express CD40L, which matures the endogenous DCs, and produce cytokines, such as IL-2, which activates NK cells. These findings suggest that DC vaccination can sustain long-term innate NK cell immunity but requires the participation of the adaptive immune system.
authors: Research Unit for Cellular Immunotherapy, Research Center for Allergy and Immunology, The Institute of Physical and Chemical Research (RIKEN), Yokohama, Kanagawa 230-0045, Japan.
authors: Kanako
authors: K
authors: Shimizu
authors: Miki
authors: M
authors: Asakura
authors: Shin-ichiro
authors: S
authors: Fujii
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D023201:CD40 Ligand / Q000032:analysis; D019496:Cancer Vaccines / Q000276:immunology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D054357:Chemokine CXCL10 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D007156:Immunologic Memory; D007376:Interleukin-2 / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016133:Polymerase Chain Reaction; D012513:Sarcoma, Experimental / Q000276:immunology* / Q000517:prevention & control; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D019496:Cancer Vaccines; D054357:Chemokine CXCL10; C485433:Cxcl10 protein, mouse; D016207:Cytokines; D007376:Interleukin-2; D023201:CD40 Ligand