title: Alterations of costimulatory molecules and instructive cytokines expressed by dendritic cells in the microenvironment of an endogenous mouse lymphoma.
abstract: Costimulatory surface molecules and instructive cytokines expressed by dendritic cells (DCs) determine the outcome of an immune response. In malignant disease, DCs are often functionally compromised. In most tumors studied so far, the deficient induction of effective T cell responses has been associated with a blockade of DC maturation, but little has been known on DCs infiltrating malignant B cell lymphoma. Here, we investigated for the first time the phenotypic and functional status of DCs in B cell lymphoma, and we analyzed the network of DCs, tumor cells, natural killer (NK) cells and cytokines present in the tumor micromilieu. Therefor, we used an endogenous myc-transgenic mouse lymphoma model, because transplanted tumor cells foster an IFN-γ-driven Th1 antitumor response rather than an immunosuppressive environment, which is observed in autochthonous neoplasias. Lymphoma-infiltrating DCs showed a mature phenotype and a Th2-inducing cytokine pattern. This situation is in contrast to most human malignancies and mouse models described. Cellular contacts between DCs and tumor cells, which involved CD62L on the lymphoma, caused upregulation of costimulatory molecules, whereas IL-10 primarily derived from lymphoma cells induced an IL-12/IL-10 shift in DCs. Thus, alteration of costimulatory molecules and instructive cytokines was mediated by distinct mechanisms. Normal NK cells were able to additionally modulate DC maturation but this effect was absent in the lymphoma environment where IFN-γ production by NK cells was severely impaired. These data are relevant for establishing novel immunotherapeutic approaches against B cell lymphoma.
authors.affiliation: Institut für Molekulare Immunologie, Helmholtz-Zentrum München, Marchioninistr. 25, 81377, Munich, Germany.
authors.forename: Marcella
authors.initials: M
authors.lastname: Naujoks
authors.forename: Jakob
authors.initials: J
authors.lastname: Weiß
authors.forename: Tanja
authors.initials: T
authors.lastname: Riedel
authors.forename: Nadine
authors.initials: N
authors.lastname: Hömberg
authors.forename: Margarethe
authors.initials: M
authors.lastname: Przewoznik
authors.forename: Elfriede
authors.initials: E
authors.lastname: Noessner
authors.forename: Martin
authors.initials: M
authors.lastname: Röcken
authors.forename: Ralph
authors.initials: R
authors.lastname: Mocikat
mesh_terms: D000818:Animals; D041702:BALB 3T3 Cells; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D005434:Flow Cytometry; D016259:Genes, myc; D007694:Killer Cells, Natural / Q000276:immunology*; D016393:Lymphoma, B-Cell / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009857:Oncogenes; D059016:Tumor Microenvironment / Q000276:immunology*
chemical_list: D016207:Cytokines