Journal
BLOOD
Volume 112, Issue 8, Pages 3339-3347Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2008-01-134783
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Funding
- Wilhelm Sander-Stiftung
- Berliner Krebsgesellschaft
- Deutsche Forschungsgemeinschaft
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The malignant Hodgkin/Reed-Sternberg (HRS) cells of classical Hodgkin lymphoma (HL) are derived from mature B cells, but have lost a considerable part of the B cell-specific gene expression pattern. Consequences of such a lineage infidelity for lymphoma pathogenesis are currently not defined. Here, we report that HRS cells aberrantly express the common cytokine-receptor gamma-chain (gamma(c)) cytokine IL-21, which is usually restricted to a subset of CD4(+) T cells, and the corresponding IL-21 receptor. We demonstrate that IL-21 activates STAT3 in HRS cells, up-regulates STAT3 target genes, and protects HRS cells from CD95 death receptor induced apoptosis. Furthermore, IL-21 is involved in up-regulation of the CC chemokine macrophage-inflammatory protein-3 alpha (MIP-3 alpha) inHRScells. MIP-3 alpha in turn attracts CCR6(+)CD4(+)CD25(+)FoxP3(+)CD127(lo) regulatory T cells toward HRS cells, which might favor their immune escape. Together, these data support the concept that aberrant expression of B lineage-inappropriate genes plays an important role for the biology of HL tumor cells.
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