title: Tumour-loaded α-type 1-polarized dendritic cells from patients with chronic lymphocytic leukaemia produce a superior NK-, NKT- and CD8+ T cell-attracting chemokine profile.
abstract: Tumour-loaded dendritic cells (DCs) from patients with chronic lymphocytic leukaemia (CLL) matured using an α-type 1-polarized DC cocktail (IL-1β/TNF-α/IFN-α/IFN-γ/poly-I:C;αDC1) were recently shown to induce more functional CD8(+) T cells against autologous tumour cells in vitro than DCs matured with the 'standard' cocktail (IL-1β/TNF-α/IL-6/PGE(2) ;PGE(2) DCs). However, the ability of vaccine DCs to induce a type 1-polarized immune response in vivo probably relies on additional features, including their ability to induce a CXCR3-dependent recruitment of NK cells into vaccine-draining lymph nodes. Moreover, their guiding of rare tumour-specific CD8(+) T cells to sites of DC-CD4(+) T cell interactions by secretion of CCL3 and CCL4 is needed. We therefore analysed the chemokine profile and the lymphocyte-attracting ability in vitro of monocyte-derived PGE(2) DCs and αDC1s from patients with CLL. αDC1s produced much higher levels of CXCR3 ligands (CXCL9/CXCL10/CXCL11) than PGE(2) DCs. Functional studies further demonstrated that αDC1s were superior recruiters of both NK and NKT cells. Moreover, αDC1s produced higher levels of CCL3/CCL4 upon CD40 ligation. These findings suggest that functional αDC1s, derived from patients with CLL, produce a desirable NK-, NKT- and CD8(+) T cell-attracting chemokine profile which may favour a guided and Th1-deviated priming of CD8(+) T cells, supporting the idea that αDC1-based vaccines have a higher immunotherapeutic potential than PGE(2) DCs.
authors: Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, SwedenDepartment of Clinical Chemistry and Transfusion Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, SwedenSection of Haematology and Coagulation, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, SwedenDepartment of Microbiology and Immunology all at Sahlgrenska University Hospital, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, SwedenDepartment of Clinical Immunology, Akademiska University Hospital, Uppsala University, Sweden.
authors: Karin
authors: K
authors: Gustafsson
authors: Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, SwedenDepartment of Clinical Chemistry and Transfusion Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, SwedenSection of Haematology and Coagulation, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, SwedenDepartment of Microbiology and Immunology all at Sahlgrenska University Hospital, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, SwedenDepartment of Clinical Immunology, Akademiska University Hospital, Uppsala University, Sweden.
authors: Katarina
authors: K
authors: Junevik
authors: Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, SwedenDepartment of Clinical Chemistry and Transfusion Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, SwedenSection of Haematology and Coagulation, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, SwedenDepartment of Microbiology and Immunology all at Sahlgrenska University Hospital, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, SwedenDepartment of Clinical Immunology, Akademiska University Hospital, Uppsala University, Sweden.
authors: Olle
authors: O
authors: Werlenius
authors: Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, SwedenDepartment of Clinical Chemistry and Transfusion Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, SwedenSection of Haematology and Coagulation, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, SwedenDepartment of Microbiology and Immunology all at Sahlgrenska University Hospital, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, SwedenDepartment of Clinical Immunology, Akademiska University Hospital, Uppsala University, Sweden.
authors: Sandra
authors: S
authors: Holmgren
authors: Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, SwedenDepartment of Clinical Chemistry and Transfusion Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, SwedenSection of Haematology and Coagulation, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, SwedenDepartment of Microbiology and Immunology all at Sahlgrenska University Hospital, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, SwedenDepartment of Clinical Immunology, Akademiska University Hospital, Uppsala University, Sweden.
authors: Alex
authors: A
authors: Karlsson-Parra
authors: Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, SwedenDepartment of Clinical Chemistry and Transfusion Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, SwedenSection of Haematology and Coagulation, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, SwedenDepartment of Microbiology and Immunology all at Sahlgrenska University Hospital, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, SwedenDepartment of Clinical Immunology, Akademiska University Hospital, Uppsala University, Sweden.
authors: Per-Ola
authors: PO
authors: Andersson