Journal: Frontiers in Cellular and Infection Microbiology

Article Title: Lenalidomide potentially reduced the level of cell- associated HIV RNA and improved persistent inflammation in patients with HIV-associated cryptococcal meningitis a pilot study

doi: 10.3389/fcimb.2022.954814

Figure Lengend Snippet: Longitudinal dynamics of (A) TNF-α, (B) IL-6, (C) CRP, and (D) D-dimer during the 48-week lenalidomide therapy. Participants are color-coded. P -values representing the difference between the time points are shown on the right side of the graphs.

Article Snippet: The CD8-depleted PBMCs were cultured in complete RPMI 1640 medium supplemented with 10% fetal bovine serum and 1% penicillin-streptomycin and stimulated with 100 ng/mL lipopolysaccharide (LPS, Sigma-Aldrich,USA) in the presence or absence of 1 μM lenalidomide (MCE,USA) for 5 days.

Techniques:

Journal: Frontiers in Cellular and Infection Microbiology

Article Title: Lenalidomide potentially reduced the level of cell- associated HIV RNA and improved persistent inflammation in patients with HIV-associated cryptococcal meningitis a pilot study

doi: 10.3389/fcimb.2022.954814

Figure Lengend Snippet: Longitudinal dynamics of (A) HIV-1 RNA, (B) CA HIV-1 RNA, (C) CA HIV-1 RNA/total HIV-1 DNA, and (D) total HIV-1 DNA during the 48-week lenalidomide therapy. Participants are color-coded. P -values representing the difference between the time points are shown on the right side of the graphs.

Article Snippet: The CD8-depleted PBMCs were cultured in complete RPMI 1640 medium supplemented with 10% fetal bovine serum and 1% penicillin-streptomycin and stimulated with 100 ng/mL lipopolysaccharide (LPS, Sigma-Aldrich,USA) in the presence or absence of 1 μM lenalidomide (MCE,USA) for 5 days.

Techniques:

Journal: Frontiers in Cellular and Infection Microbiology

Article Title: Lenalidomide potentially reduced the level of cell- associated HIV RNA and improved persistent inflammation in patients with HIV-associated cryptococcal meningitis a pilot study

doi: 10.3389/fcimb.2022.954814

Figure Lengend Snippet: Spearman correlations between CA HIV-1 RNA and CRP, IL-6, TNF-α, and D-dimer. (A–C) , CRP, IL-6, and TNF-α were significantly correlated with CA HIV RNA levels after lenalidomide therapy. (D) , The correlation between D-dimer and CA HIV-1 RNA was not significant.

Article Snippet: The CD8-depleted PBMCs were cultured in complete RPMI 1640 medium supplemented with 10% fetal bovine serum and 1% penicillin-streptomycin and stimulated with 100 ng/mL lipopolysaccharide (LPS, Sigma-Aldrich,USA) in the presence or absence of 1 μM lenalidomide (MCE,USA) for 5 days.

Techniques:

Journal: Frontiers in Cellular and Infection Microbiology

Article Title: Lenalidomide potentially reduced the level of cell- associated HIV RNA and improved persistent inflammation in patients with HIV-associated cryptococcal meningitis a pilot study

doi: 10.3389/fcimb.2022.954814

Figure Lengend Snippet: Longitudinal dynamics of (A, B) CD4 + and (C, D) CD8 + T cell activation at 24W of lenalidomide therapy. Participants are color-coded. P -values representing the values of the change during lenalidomide treatment are shown on the right side of the graphs.

Article Snippet: The CD8-depleted PBMCs were cultured in complete RPMI 1640 medium supplemented with 10% fetal bovine serum and 1% penicillin-streptomycin and stimulated with 100 ng/mL lipopolysaccharide (LPS, Sigma-Aldrich,USA) in the presence or absence of 1 μM lenalidomide (MCE,USA) for 5 days.

Techniques: Activation Assay

Journal: Frontiers in Cellular and Infection Microbiology

Article Title: Lenalidomide potentially reduced the level of cell- associated HIV RNA and improved persistent inflammation in patients with HIV-associated cryptococcal meningitis a pilot study

doi: 10.3389/fcimb.2022.954814

Figure Lengend Snippet: Lenalidomide inhibited HIV-1 reactivation in CD8-depleted PBMCs. CD8-depleted PBMCs were treated with TNF-α and LPS with or without lenalidomide for 5 days, or with the solvent control. (A, B) , HIV core antigen was determined by flow cytometry in the PBMCs. (C) , CA HIV RNA of CD8-depleted PBMCs was measured by RT-PCR. (D) , Cytokine levels in the supernatants were determined by flow cytometry. * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001.

Article Snippet: The CD8-depleted PBMCs were cultured in complete RPMI 1640 medium supplemented with 10% fetal bovine serum and 1% penicillin-streptomycin and stimulated with 100 ng/mL lipopolysaccharide (LPS, Sigma-Aldrich,USA) in the presence or absence of 1 μM lenalidomide (MCE,USA) for 5 days.

Techniques: Solvent, Control, Flow Cytometry, Reverse Transcription Polymerase Chain Reaction

Journal: Pulmonary Circulation

Article Title: Sevoflurane inhibits cardiac function in pulmonary fibrosis mice through the TLR4 signaling pathway

doi: 10.1177/2045894018800702

Figure Lengend Snippet: The changes of HR and EF after sevoflurane inhalation in pulmonary fibrosis mice treated with lenalidomide or DMSO. WT-PF+Lenalidomide: pulomary fibrosis mice treated with lenalidomide; WT-PF+DMSO: pulomary fibrosis mice treated with DMSO. Values are presented as mean ± SD (n = 6 for each group). * P < 0.05, ** P < 0.01, *** P < 0.001, when T1 is compared with T0; # P < 0.05, ### P < 0.001, when T2 is compared with T0.

Article Snippet: Pulmonary fibrosis WT mice were given the TNF-α inhibitor lenalidomide (50 mg/kg/d, Selleck Chemicals LLC, Houston, TX, USA) intragastrically for three days, while the control group was treated with 1% dimethyl sulfoxide (DMSO).

Techniques:

Journal: Cancers

Article Title: LAG-3 Blockade with Relatlimab (BMS-986016) Restores Anti-Leukemic Responses in Chronic Lymphocytic Leukemia

doi: 10.3390/cancers13092112

Figure Lengend Snippet: LAG-3 expression is upregulated on leukemic cells from patients with CLL. LAG-3 surface expression was evaluated on PBMCs from patients with CLL ( n = 61) and HD ( n = 20) by flow cytometry. ( A ) Representative dot plot for LAG-3+ CD19+ analysis; ( B ) Comparison of LAG-3 expression (MFI ± SEM) between leukemic cells and B lymphocytes from HD; ( C ) Percentage of LAG-3+ leukemic cells compared to B cells from HD; ( D ) Sera levels of sLAG-3 were evaluated in 28 patients with CLL and 12 HD; ( E ) In silico analysis of the effect of the indicated therapies on LAG3 mRNA expression in leukemic cells. GSE112953 and GSE58211 from GEO database were included. Each dot represents an individual sample (FC: fludarabine-chlorambucil, R-FC: Rituximab- fludarabine-chlorambucil, LND: lenalidomide). ** p < 0.01 and **** p < 0.0001.

Article Snippet: PBMCs from patients with CLL were treated with the blocking anti-LAG-3 mAb relatlimab (BMS-986016, kindly provided by Bristol-Myers Squibb), or control IgG (10 μg/mL) for 72 h or a week, alone or in combination with 10 μM lenalidomide (LND) (Santa Cruz Biotechnology, Dallas, TX, USA).

Techniques: Expressing, Flow Cytometry, Comparison, In Silico

Journal: Cancers

Article Title: LAG-3 Blockade with Relatlimab (BMS-986016) Restores Anti-Leukemic Responses in Chronic Lymphocytic Leukemia

doi: 10.3390/cancers13092112

Figure Lengend Snippet: Treatment with relatlimab depletes leukemic cells. ( A ) PBMCs from 26 patients with CLL were treated with relatlimab or isotype control (10 µg/mL) and absolute leukemic cell count was performed at indicated timepoints. Bars represent the percentage of leukemic cells normalized to control; ( B ) Intracellular staining and flow cytometry analysis for Bcl-2 expression (normalized to control) were performed in PBMCs treated with relatlimab or isotype control (10 µg/mL) for 72 h or 7 days ( n = 8); ( C ) Evaluation of absolute leukemic cell count (normalized to control) in PBMCs from patients treated with relatlimab or isotype control (10 µg/mL), alone or in combination with lenalidomide (LND) (10 µM), for 72 h ( n = 12); ( D ) Effect of LAG-3 blockade on NK cell-mediated cytotoxicity was evaluated by calcein-AM assay in PBMCs from 10 patients treated with relatlimab (10 µg/mL), alone or in combination with lenalidomide (LND; 10 µM), and co-cultured with MEC-I CLL-derived cell line at 25:1 (E:T) ratio ( n = 10) for 72 h. ADCC was evaluated by pre-treating target MEC-I cells with rituximab (10 µg/mL). * p < 0.05, ** p < 0.01 and *** p < 0.001.

Article Snippet: PBMCs from patients with CLL were treated with the blocking anti-LAG-3 mAb relatlimab (BMS-986016, kindly provided by Bristol-Myers Squibb), or control IgG (10 μg/mL) for 72 h or a week, alone or in combination with 10 μM lenalidomide (LND) (Santa Cruz Biotechnology, Dallas, TX, USA).

Techniques: Control, Cell Counting, Staining, Flow Cytometry, Expressing, Calcein AM Assay, Cell Culture, Derivative Assay

Journal: Cancers

Article Title: LAG-3 Blockade with Relatlimab (BMS-986016) Restores Anti-Leukemic Responses in Chronic Lymphocytic Leukemia

doi: 10.3390/cancers13092112

Figure Lengend Snippet: Relatlimab enhances cytokine production by T lymphocytes. ( A ) Representative histogram showing the effect of LAG-3 blockade, alone or in combination with lenalidomide, on IL-2 production by CD4+ T cells. ( B – J ) PBMCs from 11 patients with CLL were treated with relatlimab or isotype control (10 µg/mL), alone or in combination with lenalidomide (LND, 10 µM), for 72 h. The percentage of T cells expressing TNF-α ( B – D ), IFN-γ ( E – G ) and IL-2 ( H – J ) was evaluated by flow cytometry. * p < 0.05, ** p < 0.01 and *** p < 0.001.

Article Snippet: PBMCs from patients with CLL were treated with the blocking anti-LAG-3 mAb relatlimab (BMS-986016, kindly provided by Bristol-Myers Squibb), or control IgG (10 μg/mL) for 72 h or a week, alone or in combination with 10 μM lenalidomide (LND) (Santa Cruz Biotechnology, Dallas, TX, USA).

Techniques: Control, Expressing, Flow Cytometry

Journal: Advances in Hematology

Article Title: Molecular Action of Lenalidomide in Lymphocytes and Hematologic Malignancies

doi: 10.1155/2012/513702

Figure Lengend Snippet: Various T-cell signaling pathways are upregulated after lenalidomide treatment. Lenalidomide is known to have no direct mitogenic activity, therefore it cannot induce proliferation directly. Upon TCR ligation, lenalidomide (LEN) increases phosphorylation of tyrosines within the intracytoplasmic tail of CD28, through an unknown mechanism, increasing downstream signaling and activation of PKC- θ , MAPK, and potentially other signaling pathways. These pathways lead to the activation of classic T-cell transcription factors like AP-1, NFAT-1, and NF- κ B that induce secretion of the T helper type 1 (Th-1) cytokines interleukin-2 (IL-2), tumor necrosis factor- α (TNF- α ), and interferon- γ (IFN- γ ). Though it is controversial which transcription factors are ultimately increased upon lenalidomide treatment (indicated by a question mark). Upregulation of these pathways potentially reverses T-cell defects, aids in breaking tolerance, and leads to greater CD4+ T-cell help to DCs, NK cells, and CD8+ T cells, augmenting eradication of the tumor cells.

Article Snippet: In addition to the specific effects of lenalidomide on T-cell signaling, our lab and others have shown that the drug alters homeostatic regulation of T cells [ ].

Techniques: Protein-Protein interactions, Activity Assay, Ligation, Phospho-proteomics, Activation Assay

Journal: Advances in Hematology

Article Title: Molecular Action of Lenalidomide in Lymphocytes and Hematologic Malignancies

doi: 10.1155/2012/513702

Figure Lengend Snippet: Lenalidomide augments direct CD8+ T-cell killing of B-CLL cells. B-CLL cells are able to evade immune detection through high levels of PDL-1, low levels of costimulatory molecules like B7-1, and a variety of immune-suppressive cytokines in the microenvironment. Lenalidomide treatment (Len) is able to overcome the immune suppression through upregulation of costimulatory molecules like CD40 and B7-1 (CD80/86) on the CLL cells, upregulation of Fas expression, as well as decreasing PDL-1. Through the alteration of surface molecule expression, as well as the increase in T-cell signaling as shown previously, lenalidomide induces better immune synapse formation allowing for increased killing by the CD8+ T cells.

Article Snippet: In addition to the specific effects of lenalidomide on T-cell signaling, our lab and others have shown that the drug alters homeostatic regulation of T cells [ ].

Techniques: Expressing

Journal: Advances in Hematology

Article Title: Molecular Action of Lenalidomide in Lymphocytes and Hematologic Malignancies

doi: 10.1155/2012/513702

Figure Lengend Snippet: Lenalidomide alone, or in combination with a variety of therapeutic monoclonal antibodies, increases NK-cell-mediated killing of multiple myeloma cells. Lenalidomide (LEN) increases IL-2 secretion from by-standing T helper cells which augments NK cell activity. Lenalidomide, as described previously, upregulates Fas expression and costimulatory molecules on MM cells leading to greater Fas-mediated apoptosis. Lenalidomide has also been shown to augment the ADCC effect of various monoclonal antibodies like Rituximab (anti-CD20), GA-101 (glycoengineered anti-CD20), and CT-011 (anti-PDL-1). CT-011 blocks PD-1 ligand on the MM cells, interfering with binding to PD-1 and inhibiting NK cell activity. Binding of the anti-CD20 antibodies to their targets on MM cells increases complement-dependent cytotoxicity (CDC), as well as NK-cell recognition and killing of the MM cells. IPH2101 is an anti-inhibitory KIR that has been shown in combination with lenalidomide to increase NK-cell killing as well, as blocking the inhibitory signals allows for NK activation and detection of the tumor cells.

Article Snippet: In addition to the specific effects of lenalidomide on T-cell signaling, our lab and others have shown that the drug alters homeostatic regulation of T cells [ ].

Techniques: Bioprocessing, Activity Assay, Expressing, Binding Assay, Blocking Assay, Activation Assay