Project description:We report the single-cell RNA sequencing data obtained from BCL1 lymphoma-bearing mice treated with either isotype control, anti-CD20 mAb, anti-CD27 mAb or anti-CD20+anti-CD27 mAb together
Project description:Primary Mediastinal large B-cell lymphoma (PMBL) is a rare form of non-Hodgkin lymphoma (NHL) representing 2% of mature B-cell NHL in patients less than 18 years of age.We compared the gene expression profiling between fully humanized anti-CD20 targeted monoclonal antibody recognizing a unique CD20 type II epitope, obinutuzumab and IgG or PBS treated Karpas Primary Mediastinal B-cell lymphoma (PMBL) cell line. -
Project description:Goals/objectives: to identify various gene expression in B cell subsets derived from human PBMC and cord blood Sample: human PBMC and human cord blood Cell subsets: memory B cell (CD20+CD10-CD27+), naive B cell (CD20+CD10-CD27-), CD21lo transitional B cell (CD20+CD10+CD27-CD21lo), CD21hi transitional B cell (CD20+CD10+CD27-CD21hi) Number of sample: PBMC (pooled from 2 donors), cord blood (pooled from 2-3 donors) Number of repeats: 2 Microarray: Affymetrix HU133Plus2 RNA extraction: Trizol (Invitrogen) RNA preparation/hybridization: All according to affymetrix protocol
Project description:Using both global and conditional knockout mice, we demonstrated that the transcription factor Basic Helix-Loop-Helix Family Member E40 (BHLHE40/DEC1) is required in T cells for rejection of mouse syngeneic tumors upon immune checkpoint therapy (ICT) with anti-PD-1 or anti-CTLA-4 monoclonal antibody (mAb) treatment. Using single cell RNA sequencing (scRNAseq) we profiled intratumoral CD45+ cells from syngeneic mouse sarcomas that (a) grow progressively with control treatment in either Bhlhe40+/+ or Bhlhe40-/- tumor-bearing mice, (b) reject following anti-PD-1 or anti-CTLA-4 ICT in Bhlhe40+/+ tumor-bearing mice, or (c) grow progressively following anti-PD-1 or anti-CTLA-4 in Bhlhe40-/- mice. We performed two separate scRNAseq experiments with the same conditions but harvested tumors on either day 9 post-tumor transplant or day 11 post-tumor transplant. The groups were as follows: (1) Control mAb Bhlhe40+/+, (2) Control mAb Bhlhe40-/-, (3) anti-PD-1 Bhlhe40+/+, (4) anti-PD-1 Bhlhe40-/-, (5) anti-CTLA-4 Bhlhe40+/+, and (6) anti-CTLA-4 Bhlhe40-/-. scRNAseq of intratumoral immune cells in BHLHE40-deficient mice revealed differential ICT-induced immune cell remodeling. These BHLHE40-dependent gene expression alterations were associated with altered metabolism, NF-kB signaling, and IFN- response in subpopulations of intratumoral CD4+ and CD8+ T cells. Intratumoral T cells from tumor-bearing Bhlhe40-/- mice also had higher transcript expression of the inhibitory receptor gene Tigit, along with altered transcript expression of chemokine/chemokine receptor granzyme family members. Bhlhe40-/- CD4+ and CD8+ T cells also had reduced ICT-driven IFN- production. Furthermore, BHLHE40 was required for ICT-induced remodeling of macrophages from a CX3CR1+ CD206+ subpopulation to an iNOS+ subpopulation. While anti-PD-1 or anti-CTLA-4 ICT in tumor-bearing Bhlhe40-/- mice led to tumor outgrowth—several BHLHE40-dependent changes were specific to the ICT treatment that was administered.
Project description:Objective: To investigate how anti-CD20 B cell-depleting monoclonal antibodies (ɑCD20 mAb) alter the composition and gene expression of immune cells in meningeal ectopic lymphoid tissue (mELT) and the CSF in a murine model of Multiple Sclerosis (MS). Methods: We utilized a spontaneous chronic experimental autoimmune encephalomyelitis (EAE) model of mice with mutant T and B cell receptors specific for myelin oligodendrocyte glycoprotein (MOG), which develop meningeal inflammatory infiltrates resembling those described in Multiple Sclerosis (MS). We studied the changes in cell composition and gene expression after anti-CD20 treatment in mELT and CSF.
Project description:to determine whether hydroxymethyl butyrate alters PDAC response to anti-PD1 therapy, mice bearing PANC02 tumors were treated with anti-PD1 with or without HMB supplementation
Project description:We investigated the differential regulation patterns of type I anti-CD20 monoclonal antibody (mAb) rituximab and type II obinutuzumab on a transcriptional level. Using a panel of MCL cell lines, we determined the effects of obinutuzumab and rituximab as monotherapies as well as in combination on cell viability and proliferation. Obinutuzumab induced a higher reduction in cell proliferation in each mantle cell lymphoma cell line than rituximab did. Results indicate a common pattern of expression changes after binding of anti-CD20 mAbs, but also reveal a significant difference between type I and type II treatment. Combination treatment resulted in a rituximab-like expression pattern. Many deregulated genes were associated with stress signalling, cell death, immune response and other functional clusters. Our analyses identified different and antibody-specific downstream expression patterns of obinutuzumab and rituximab, which may represent the molecular basis of the superior effect of obinutuzumab in comparison to rituximab.
Project description:Type 1 diabetes (T1D) results from autoimmune destruction of β cells in the pancreas. Protein tyrosine phosphatases (PTPs) are candidate genes for T1D and play a key role in autoimmune disease development and β-cell function. Here, we assessed the global protein and individual PTP profile in the pancreas of diabetic NOD mice treated with anti-CD3 mAb and IL-1RA combination therapy. The treatment reversed hyperglycemia compared to the anti-CD3 alone control group. We observed enhanced expression of PTPN2, a T1D candidate gene, and endoplasmic reticulum (ER) chaperones in the islets from cured mice.
Project description:An LC-MS/MS based phosphoproteomics study that characterizes the signaling processes downstream of the B-cell receptor and how they are differentially regulated following treatment with anti-CD20 monoclonal antibodies in B-cell lymphoma.
