Abstract
Multiple myeloma (MM) is a proliferation of tumoral plasma B cells that is still incurable. Natural killer (NK) cells can recognize and kill MM cells in vitro and can limit MM growth in vivo. Previous reports have shown that NK cell function is impaired during MM progression and suggested that treatment with immunomodulatory drugs (IMIDs) such as lenalidomide (LEN) could enhance it. However, the effects of IMIDs on NK cells have been tested mostly in vitro or in preclinical models and supporting evidence of their effect in vivo in patients is lacking. Here, we monitored NK cell activity in blood samples from 10 MM patients starting after frontline induction chemotherapy (CTX) consisting either of association of bortezomib–lenalidomide–dexamethasone (Velcade Revlimid Dexamethasone) or autologous stem-cell transplantation (SCT). We also monitored NK cell activity longitudinally each month during 1 year, after maintenance therapy with LEN. Following frontline chemotherapy, peripheral NK cells displayed a very immature phenotype and retained poor reactivity toward target cells ex vivo. Upon maintenance treatment with LEN, we observed a progressive normalization of NK cell maturation, likely caused by discontinuation of chemotherapy. However, LEN treatment neither activated NK cells nor improved their capacity to degranulate or to secrete IFN-γ or MIP1-β following stimulation with MHC-I-deficient or antibody-coated target cells. Upon LEN discontinuation, there was no reduction of NK cell effector function either. These results caution against the use of LEN as single therapy to improve NK cell activity in patients with cancer and call for more preclinical assessments of the potential of IMIDs in NK cell activation.
Highlights
Multiple myeloma (MM) is a genetically heterogeneous disease characterized by a proliferation of tumoral plasma B cells [1]
Degranulation as measured by CD107a exposure and IFN-γ, TNF-α, and MIP1-β secretion were measured upon a 4-h ex vivo culture without stimulus or in the presence of K562 cells or Granta B cells coated with rituximab anti-CD20 antibody, to measure natural cytotoxicity and antibody dependent cell-mediated cytotoxicity (ADCC), respectively
We could not detect any signs of Natural killer (NK) cell activation or any improvement of their functional capacity in patients undergoing several cycles of LEN treatment
Summary
Multiple myeloma (MM) is a genetically heterogeneous disease characterized by a proliferation of tumoral plasma B cells [1]. MM is among the most frequent hematologic malignancies and induces anemia, bone lesions, and renal dysfunction. Despite the emergence of several novel dedicated therapies, MM remains of poor prognosis, because most patients become refractory to treatments [2]. MM frequently progresses from a premalignant stage called monoclonal gammopathy of undetermined. Impact of LEN on NK cells significance. Patients present either smoldering (or indolent) asymptomatic MM or symptomatic MM with organ damages that require immediate treatment. Efforts are underway to understand genetic and other factors that influence progression of indolent to active MM and to find treatments that could prevent or delay this progression [1]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
