Lenalidomide triggers T-cell effector ...
Document type :
Article dans une revue scientifique: Article original
PMID :
Permalink :
Title :
Lenalidomide triggers T-cell effector functions in vivo in patients with follicular lymphoma.
Author(s) :
Ménard, Cédric [Auteur]
Rossille, Delphine [Auteur]
Dulong, Joëlle [Auteur]
Nguyen, Tien Tuan [Auteur]
Papa, Ilenia [Auteur]
Latour, Maëlle [Auteur]
Bescher, Nadège [Auteur]
Bezier, Isabelle [Auteur]
Chouteau, Myriam [Auteur]
Fest, Thierry [Auteur]
Houot, Roch [Auteur]
Microenvironment, Cell Differentiation, Immunology and Cancer [MICMAC]
Morschhauser, Franck [Auteur]
Groupe de Recherche sur les formes Injectables et les Technologies Associées (GRITA) - ULR 7365
Tarte, K. [Auteur]
Rossille, Delphine [Auteur]
Dulong, Joëlle [Auteur]
Nguyen, Tien Tuan [Auteur]
Papa, Ilenia [Auteur]
Latour, Maëlle [Auteur]
Bescher, Nadège [Auteur]
Bezier, Isabelle [Auteur]
Chouteau, Myriam [Auteur]
Fest, Thierry [Auteur]
Houot, Roch [Auteur]
Microenvironment, Cell Differentiation, Immunology and Cancer [MICMAC]
Morschhauser, Franck [Auteur]

Groupe de Recherche sur les formes Injectables et les Technologies Associées (GRITA) - ULR 7365
Tarte, K. [Auteur]
Journal title :
Blood Advances
Abbreviated title :
Blood Adv
Volume number :
5
Pages :
2063-2074
Publisher :
American Society of Hematology
Publication date :
2021-04-21
ISSN :
2473-9537
HAL domain(s) :
Sciences du Vivant [q-bio]
English abstract : [en]
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 ...
Show more >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.Show less >
Show more >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.Show less >
Language :
Anglais
Audience :
Internationale
Administrative institution(s) :
Université de Lille
CHU Lille
CHU Lille
Collections :
Submission date :
2023-05-25T03:09:12Z
2023-08-30T11:48:02Z
2023-08-30T11:48:02Z