8th International Symposium on Hodgkin Lymphoma, Cologne, Germany, October 23–26, 2010

摘要

Background. Toll like receptors (TLRs) have been implicated in the pathogenesis of many hematological malignancies by modulating the immune response and by providing tumor cell survival signals. In clas- sical Hodgkin lymphoma (cHL), which is characterized by an extensive reactive infiltrate, the role of TLRs has not been studied yet. Methods.We tested the expression of TLR4, TLR7 and TLR9 by immunohistochem- istry on paraffin sections and expression of TLR2 on frozen sections of 19 patients diagnosed with classical Hodgkin lymphoma. The expres- sion of FoxP3 and IL17 was used to count regulatory T cells and Th17 cells respectively. Ligation of TLRs on cHL cell lines was performed to study the functionality of the TLRs with respect to induction of cytokine production, cell growth, and phosphorylation of downstream targets. Results. TLR4, TLR7 and TLR9 were expressed in Hodgkin Reed-Stern- berg (HRS) cells in a variable percentage of cHL cases, whereas TLR2 was consistently negative. In contrast to their pathogenic role in other malig- nancies, we observed only minor effects upon ligation of TLR4, TLR7 and TLR9 in cHL cell lines. There was no correlation of TLR expression with presence of regulatory T cells or Th17 cells and also not with expression of HLA class I and class II in HRS cells in patient tissue sam- ples. Ligation of TLR4, TLR7 and TLR9 in cHL cell lines did not induce production of IL-1, IL-6 or IL-10 and induced only minor effects on cell growth. The most pronounced effect on cell growth was observed upon ligation of TLR7 in KMH2 cells, which was associated with upregula- tion of p-JNK1/2 and p-Erk1/2. Triggering of TLR9 suppressed cell growth in some cHL cell lines. Conclusion.We found expression of TLR4, TLR7 and TLR9 in HRS cells, whereas TLR2 was not expressed. The responsiveness to ligation is limited with no effect on cytokine produc- tion and only a moderate effect on cell growth in cHL cell lines. In cHL tissue no association of TLR expression was observed with presence of regulatory T and Th17 cells or expression of HLA. These findings indi- cate a hyporesponsive state of these three TLRs in cHL.