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Lenalidomide triggers T-cell effector functions in vivo in patients with follicular lymphoma

Abstract : The immunomodulatory drug lenalidomide is used in patients with follicular lymphoma (FL) with the aim of stimulating T-cell antitumor immune response. However, little is known about the effects of lenalidomide on T-cell biology in vivo in patients with FL. We thus undertook an extensive longitudinal immunologic study, including phenotypic, transcriptomic, and functional analyses, on 44 first-line and 27 relapsed/refractory patients enrolled in the GALEN trial (Obinutuzumab Combined With Lenalidomide for Relapsed or Refractory Follicular B-Cell Lymphoma) to test the efficacy of lenalidomide and obinutuzumab combination in patients with FL. Lenalidomide rapidly and transiently induced an activated T-cell phenotype, including HLA-DR, Tim-3, CD137, and programmed cell death protein 1 (PD-1) upregulation. Furthermore, sequential RNA-sequencing of sorted PD-1+ and PD-1- T-cell subsets revealed that lenalidomide triggered a strong enrichment for several gene signatures related to effector memory T-cell features, including proliferation, antigen receptor signaling, and immune synapse restoration; all were validated at the phenotypic level and with ex vivo functional assays. Correlative analyses pinpointed a negative clinical impact of high effector T-cell and regulatory T-cell percentages before and during treatment. Our findings bring new insight in lenalidomide mechanisms of action at work in vivo and will fuel a new rationale for the design of combination therapies.
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https://hal-univ-rennes1.archives-ouvertes.fr/hal-03267824
Contributor : Laurent Jonchère Connect in order to contact the contributor
Submitted on : Tuesday, June 22, 2021 - 4:45:17 PM
Last modification on : Monday, October 11, 2021 - 3:47:24 PM

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Cédric Ménard, Delphine Rossille, Joelle Dulong, Tien-Tuan Nguyen, Ilenia Papa, et al.. Lenalidomide triggers T-cell effector functions in vivo in patients with follicular lymphoma. Blood Advances, The American Society of Hematology, 2021, 5 (8), pp.2063-2074. ⟨10.1182/bloodadvances.2020003774⟩. ⟨hal-03267824⟩

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