Loss of the Immune Checkpoint CD85j/LILRB1 on Malignant Plasma Cells Contributes to Immune Escape in Multiple Myeloma
Por:
Lozano, E, Diaz, T, Mena, MP, Sune, G, Calvo, X, Calderon, M, Perez-Amill, L, Rodriguez, V, Perez-Galan, P, Roue, G, Cibeira, MT, Rosinol, L, Isola, I, Rodriguez-Lobato, LG, Martin-Antonio, B, Blade, J and De Larrea, CF
Publicada:
15 abr 2018
Resumen:
Mechanisms of immune regulation may control proliferation of aberrant plasma cells (PCs) in patients with monoclonal gammopathy of undetermined significance (MGUS) preventing progression to active multiple myeloma (MM). We hypothesized that CD85j (LILRB1), an inhibitory immune checkpoint for B cell function, may play a role in MM pathogenesis. In this study, we report that patients with active MM had significantly lower levels of CD85j and its ligand S100A9. Decreased CD85j expression could also be detected in the premalignant condition MGUS, suggesting that loss of CD85j may be an early event promoting tumor immune escape. To gain insight into the molecular mechanisms underlying CD85j functions, we next enforced expression of CD85j in human myeloma cell lines by lentiviral transduction. Interestingly, gene expression profiling of CD85j-overexpressing cells revealed a set of downregulated genes with crucial functions in MM pathogenesis. Furthermore, in vitro functional assays demonstrated that CD85j overexpression increased susceptibility to T cell- and NK-mediated killing. Consistently, ligation of CD85j decreased the number of PCs from individuals with MGUS but not from patients with MM. In conclusion, downregulation of inhibitory immune checkpoints on malignant PCs may provide a novel mechanism of immune escape associated with myeloma pathogenesis.
Filiaciones:
Lozano, E:
Univ Barcelona, August Pi i Sunyer Biomed Res Inst, Hosp Clin, Dept Hematol,Amyloidosis & Myeloma Unit, E-08036 Barcelona, Spain
August Pi i Sunyer Biomed Res Inst, Div Hematol & Oncol, Barcelona 08036, Spain
Diaz, T:
Univ Barcelona, August Pi i Sunyer Biomed Res Inst, Hosp Clin, Dept Hematol,Amyloidosis & Myeloma Unit, E-08036 Barcelona, Spain
August Pi i Sunyer Biomed Res Inst, Div Hematol & Oncol, Barcelona 08036, Spain
Mena, MP:
Univ Barcelona, August Pi i Sunyer Biomed Res Inst, Hosp Clin, Dept Hematol,Amyloidosis & Myeloma Unit, E-08036 Barcelona, Spain
August Pi i Sunyer Biomed Res Inst, Div Hematol & Oncol, Barcelona 08036, Spain
Sune, G:
Univ Barcelona, August Pi i Sunyer Biomed Res Inst, Hosp Clin, Dept Hematol,Amyloidosis & Myeloma Unit, E-08036 Barcelona, Spain
Univ Barcelona, Josep Carreras Leukaemia Res Inst, E-08036 Barcelona, Spain
Calvo, X:
Univ Barcelona, August Pi i Sunyer Biomed Res Inst, Hosp Clin, Dept Hematol,Amyloidosis & Myeloma Unit, E-08036 Barcelona, Spain
Calderon, M:
Univ Barcelona, August Pi i Sunyer Biomed Res Inst, Hosp Clin, Dept Hematol,Amyloidosis & Myeloma Unit, E-08036 Barcelona, Spain
August Pi i Sunyer Biomed Res Inst, Div Hematol & Oncol, Barcelona 08036, Spain
Perez-Amill, L:
Univ Barcelona, August Pi i Sunyer Biomed Res Inst, Hosp Clin, Dept Hematol,Amyloidosis & Myeloma Unit, E-08036 Barcelona, Spain
Univ Barcelona, Josep Carreras Leukaemia Res Inst, E-08036 Barcelona, Spain
Rodriguez, V:
August Pi i Sunyer Biomed Res Inst, Div Hematol & Oncol, Barcelona 08036, Spain
Perez-Galan, P:
August Pi i Sunyer Biomed Res Inst, Div Hematol & Oncol, Barcelona 08036, Spain
Roue, G:
August Pi i Sunyer Biomed Res Inst, Div Hematol & Oncol, Barcelona 08036, Spain
Vall Hebron Univ Hosp, Vall Hebron Inst Oncol, Dept Hematol, Lab Expt Hematol, Barcelona 08035, Spain
Cibeira, MT:
Univ Barcelona, August Pi i Sunyer Biomed Res Inst, Hosp Clin, Dept Hematol,Amyloidosis & Myeloma Unit, E-08036 Barcelona, Spain
Rosinol, L:
Univ Barcelona, August Pi i Sunyer Biomed Res Inst, Hosp Clin, Dept Hematol,Amyloidosis & Myeloma Unit, E-08036 Barcelona, Spain
Isola, I:
Univ Barcelona, August Pi i Sunyer Biomed Res Inst, Hosp Clin, Dept Hematol,Amyloidosis & Myeloma Unit, E-08036 Barcelona, Spain
Rodriguez-Lobato, LG:
Univ Barcelona, August Pi i Sunyer Biomed Res Inst, Hosp Clin, Dept Hematol,Amyloidosis & Myeloma Unit, E-08036 Barcelona, Spain
Martin-Antonio, B:
Univ Barcelona, August Pi i Sunyer Biomed Res Inst, Hosp Clin, Dept Hematol,Amyloidosis & Myeloma Unit, E-08036 Barcelona, Spain
Univ Barcelona, Josep Carreras Leukaemia Res Inst, E-08036 Barcelona, Spain
:
Univ Barcelona, August Pi i Sunyer Biomed Res Inst, Hosp Clin, Dept Hematol,Amyloidosis & Myeloma Unit, E-08036 Barcelona, Spain
Univ Barcelona, Josep Carreras Leukaemia Res Inst, E-08036 Barcelona, Spain
De Larrea, CF:
Univ Barcelona, August Pi i Sunyer Biomed Res Inst, Hosp Clin, Dept Hematol,Amyloidosis & Myeloma Unit, E-08036 Barcelona, Spain
August Pi i Sunyer Biomed Res Inst, Div Hematol & Oncol, Barcelona 08036, Spain
Univ Barcelona, Josep Carreras Leukaemia Res Inst, E-08036 Barcelona, Spain
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