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.