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The Th17 cell percentage was lower in patients with a worse prognosis and at a more advanced clinical stage and in contrast, the percentage of T regulatory cells was increased in patients at advanced stages of lymphoma, compared to earlier stages

The Th17 cell percentage was lower in patients with a worse prognosis and at a more advanced clinical stage and in contrast, the percentage of T regulatory cells was increased in patients at advanced stages of lymphoma, compared to earlier stages. effects of T cell subsets in B-cell lymphoma immunity, with iNKT and Th17 inhibiting and T regulatory cells enhancing tumor growth. These alterations may be caused by malignant B-cells, however there may also be an axis of inverse feedback between T regulatory cells and their conversation with Th17 and iNKT cells. (45), Th17 cell numbers were lower in malignant B-cell lymphoma lymph nodes than in benign lymph nodes, and peripheral blood and tonsils of healthy individuals. Frequencies of IL-17 producing CD4+ T cells were lower in patients with FL, MZL and DLBCL compared to MCL, MALT and CLL/SLL (45). In the study of Galand (46), there was an adverse correlation between IL-17 production by Th17 cells in tumor tissue and tumor burden in mice primary intraocular B-cell L-701324 lymphoma, suggesting a protective effect of this cell population from tumor development (46). In opposition to iNKT and Th17 cells, circulatory Treg frequencies were increased in patients with B-NHL compared to healthy control and their higher numbers in more advanced stages of lymphoma suggest a supportive role in tumor development. These data are in line with earlier studies showing increased frequencies of Treg in peripheral blood of patients diagnosed with B-NHL (47,48) that correlated with tumor burden (49). Immunosupressive effect of Tregs on anti-tumor L-701324 T-cell responses in lymphoma was exhibited in several studies (49C52). The role of T regulatory cells in B-cell lymphoma is usually, however ambiguous, because Tregs can also inhibit B-cell lymphoma growth in different mechanisms (53,54) and high tumor infiltrating Tregs were found to L-701324 correlate with good prognosis in patients with B-NHL (55,56). In the present study, except the higher numbers of Tregs in more advanced clinical stages of lymphoma, we have also found an inverse correlation between circulatory Th17 and Treg cell percentages that might result from the effect of malignant B-cells on T cell differentiation-inhibiting Th17 and promoting Tregs. studies revealed that malignant B-cells not only induce the conversion of CD4+CD25? T cells into Treg cells (47,56), but also skew the balance between Th17 and Treg cells inhibiting Th17 cells and up-regulating Tregs (45). Moreover, in contrast to Th1 and Th2 cells that are irreversibly differentiated, a plasticity exists between Th17 cells and Tregs, so CD25highFoxP3+ Treg might transdifferentiate into Th17 cells and vice versa depending on the presence of lineage-specific polarizing factors (57). In this study there were no differences in circulating iNKT frequencies depending on the tumor mass and we did not observed direct relationship between Tregs and iNKT cells. However lower frequencies of iNKT in the presence of higher frequencies of Tregs might suggest inhibition of iNKT differentiation by Tregs. This suppressive effect of Tregs on iNKT proliferation and functions was therefore exhibited in studies by Azuma et. al. (58). Activated iNKT cells seem also to modulate both numbers and functions of Tregs (59). Another obtaining in L-701324 the present study was an increase of iNKT and Th17 cells after immunochemotherapy. In contrast to the Lu (26) study, where the numbers of Th17 cells in patients with B-NHL normalized after one or two cycles of chemotherapy, in our L-701324 study the significant increase was observed after the completion of R-CHOP/R-CVP therapy. In patients with disease progression both iNKT and Th17 cells were significantly lower after therapy than in patients who achieved response, again suggesting possible suppressive effect of tumor on these cell populations. However, higher iNKT and Th17 cell frequencies observed both before and after the therapy in responding patients might also indicate for their important contribution in achieving disease control. Interestingly, Molling (60), did not find KAL2 a restoration of iNKT numbers in patients.