Evaluation of regulatory T cells (Tregs) alterations in patients with multiple myeloma treated with bortezomib or lenalidomide plus dexamethasone: correlations with treatment outcome

Challenges for Immunotherapy in Multiple Myeloma: Bone Marrow Microenvironment-Mediated Immune Suppression and Immune Resistance

“…The frequencies of Tregs gradually increase in the BM-ME from progression of MGUS to overt MM disease [18][19][20][21]. Conversely, it was shown that the frequencies of Tregs decrease in MM patients after successful treatment with lenalidomide plus dexamethasone [18][19][20]. Moreover, we found inverse correlations between frequencies of recipient Tregs and their response to donor lymphocyte infusions [22].…”

“…Tregs are well known to inhibit Th1, Th17, CTL, macrophage, and DC function by cellular interactions and via secretion of suppressive cytokines, such as transforming growth factor beta (TGF-β) and IL-10 [17]. The frequencies of Tregs gradually increase in the BM-ME from progression of MGUS to overt MM disease [18][19][20][21]. Conversely, it was shown that the frequencies of Tregs decrease in MM patients after successful treatment with lenalidomide plus dexamethasone [18][19][20].…”

The Immune Microenvironment in Multiple Myeloma: Friend or Foe?

“…Furthermore, the expansion of Tregs has a negative impact on survival, which may hint at a potential therapeutic target [83]. Immunomodulatory treatments, such as lenalidomide and pomalidomide exert an anti-MM activity by inhibiting the proliferation and function of Tregs [84]. Similar to other immunosuppressive cells, such as MDSCs or Bregs, Tregs express high levels of CD38 and can be directly targeted with anti-CD38 antibodies to regulate the immune compartment and restore anti-MM T cell responses in the BM [85].…”

Visceral Leishmaniasis in 2 Patients Treated With Lenalidomide and Dexamethasone: A Possible Correlation With Blunted Immune Response

“…Using multiparametric flow cytometry analysis, we detected regulatory T cells (Tregs; CD4 + CD25highCD127neg/lowFoxP3 + cells quantified from CD4 + T cells) and lymphocyte subpopulations (CD4, CD8, CD19, natural killer [NK], NK-like T cells [NKL]) in peripheral blood at 3 different timepoints, that is, at VL onset, recession and a year after and were compared with previously published data of ours (Table 1 ). 11 …”

“… LenDex refers to 18 myeloma patients treated with LenDex in our previous study (adapted from Hadjiaggelidou et al 11 ). CD = classification determinant, CI = confidence interval, HC = healthy controls, LenDex = lenalidomide dexamethasone, MM = multiple myeloma, NK = natural killers, NKL = NK-like T cells, Tregs = T regulatory cells, VL = visceral leishmaniasis.…”