Lenalidomide potentiates CD4(+)CD25(+)Treg-related suppression of lymphoma B-cell proliferation
PBN-AR
Instytucja
Centrum Onkologii - Instytut im. Marii Skłodowskiej-Curie
Informacje podstawowe
Główny język publikacji
en
Czasopismo
Clinical and Experimental Medicine (25pkt w roku publikacji)
ISSN
1591-8890
EISSN
1591-9528
Wydawca
DOI
URL
Rok publikacji
2017
Numer zeszytu
2
Strony od-do
193-207
Numer tomu
17
Identyfikator DOI
Liczba arkuszy
0.7
Słowa kluczowe
en
Lenalidomide
Regulatory T cells
B-cell lymphoma
Streszczenia
Język
en
Treść
We have previously found that ex vivo expanded human CD4(+)CD25(+)Treg cells suppress proliferation of lymphoma B-cell lines. Here we demonstrate that the immunomodulatory drug lenalidomide potentiates suppression of lymphoma B-cell proliferation by freshly isolated CD4(+)CD25(+)Tregs, as well as suppression by Tregs expanded polyclonally in the presence of rapamycin from CD4(+)CD25(+)T cells or CD4(+)CD25(+)CD127(lo)T cells. The regulation of lymphoma cell proliferation by Tregs pre-expanded with ``third-party'' allogeneic MoDCs in the presence of rapamycin was also potentiated by lenalidomide. Lenalidomide contributed to the suppression exerted by Tregs despite concomitant downregulation of Treg proliferation. Lenalidomide did not reduce the suppression of conventional T cells by expanded Tregs. The exposure of polyclonally expanded Tregs to lenalidomide did not significantly alter their phenotype. There was no uniform pattern of lenalidomide effect on Treg-mediated regulation of lymphoma B cells freshly isolated from patients. Freshly isolated lymphoma cells activated with multimeric CD40L and IL-4 to support their survival in vitro varied in their sensitivity to lenalidomide, and the regulatory effect of Tregs on such lymphoma cells ranged from suppression to help in individual patients. Lenalidomide potentiated or attenuated Treg effects on the survival of freshly isolated lymphoma cells. A combination of lenalidomide treatment with adoptive transfer of CD4(+)CD25(+)Tregs or CD4(+)CD25(+)CD127(lo)Tregs expanded ex vivo could be used to suppress proliferation of residual lymphoma in select patients with lymphoma responsive to the regulation by Tregs and sensitive to lenalidomide.
Inne
System-identifier
COIfb93257a5d71497da0338a19f45b8a25
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