Biology subjects

Monvoisin, C.

Publications and source records attributed to Monvoisin, C..

6 recordsLinked to original sources

bioRxiv2025

Signals from the bone marrow B cell niches shape pre-leukemic fate in murine B cell acute lymphoblastic leukemia

The bone marrow (BM) microenvironment plays a key role in supporting B cell development. In acute lymphoblastic leukemia (B-ALL), the acquisition of oncogenic driver mutations blocks B cell differentiation at specific stages. When these pre-leukemic cells acquire secondary mutations, B-ALL develops. However, the role of the BM microenvironment in pre-leukemic cell fate remains unknown. Here, using a murine model of spontaneous B-ALL development, we show that disrupted pre-BCR signaling in pre-leukemic cells modifies their fate. Blocking expression of the pre-BCR ligand Galectin-1 by the microenvironment impaired pre-leukemic cell proliferation and leukemia-initiating capacity. Consequently, B-ALL development was delayed, and B-ALL had a more mature phenotype, with cells expressing a BCR. Secondary mutations were also altered by changes to Galectin-1 expression, in its absence mutations almost exclusively affected IL-7R signaling rather than both pre-BCR and IL-7R signaling. These results show that signals from BM niches can directly influence pre-leukemic B cell fate.

cancer biology↗

bioRxiv2023

Lymphoma B cells remodel bone marrow stromal cell organization and function to induce a supportive cancer-associated fibroblast network

Bone marrow (BM) involvement is a common feature of lymphomas deriving from germinal-center B cells and is associated with a bad prognosis. In particular, follicular lymphoma (FL) infiltrates the BM in 70% of cases, in association with a remodeling of surrounding tumor microenvironment. Analysis of in vitro-expanded FL mesenchymal stromal cells (MSCs) revealed an extensive alteration of BM stromal cell phenotypic, transcriptomic, and functional profiles. However, the mechanisms supporting the direct interplay between lymphoma B cells and their permissive stromal niche in situ have not been yet identified. In the current work, we identified in the BM milieu of FL patients a deregulation of soluble and extracellular matrix (ECM) components reflecting inflammation and ectopic differentiation into lymphoid-like stromal cells. We reproduced the same alterations in a murine model of lymphoma B-cell xenograft where a scRNAseq approach identified LepRpos MSCs as specifically and progressively reprogramed by tumor B-cell invasion. Analysis of FL BM collected before and after treatment confirmed that BM niche was partly dependent on the continuous contact with tumor B cells. Altogether, this work shed new lights on the kinetic and mechanisms of BM stromal niche reshaping in B-cell lymphoma.

cancer biology↗

bioRxiv2022

Single-cell profiling identifies clinically relevant interactions between tumor associated macrophages and blood endothelial cells in diffuse large B cell lymphoma

Diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL) are the two most common B-cell lymphomas and are characterized by a dynamic crosstalk between tumor B cells and a heterogeneous tumor-supportive microenvironment, including immune, endothelial, and stromal components. Although their impact on the pathogenesis and prognosis of B-cell lymphoma has been acknowledged for years, tumor-associated macrophages (TAM) have not been extensively explored in DLBCL and FL. Herein, we investigate mononuclear phagocytes (MNP) heterogeneity at the single cell level and their potential co-regulation with the stromal and endothelial compartments in B-cell lymphoma lymph nodes compared to reactive secondary lymphoid organs, using a combination of mass cytometry, single cell RNA sequencing, and in silico approaches. We reveal a co-regulation between TAM and blood endothelial cells (BEC) in lymphoma. Moreover, we identify a specific interaction between Annexin A1 (ANXA1)-expressing BEC and formyl-peptide receptors (FPR1/2)-expressing monocytes/macrophages in DLBCL, which we confirm in situ by multiplex immunofluorescence and imaging mass cytometry. This crosstalk is associated to an immunosuppressive tumor microenvironment and an adverse prognosis in DLBCL.

immunology↗

bioRxiv2021

Diverse B-cell specific transcriptional contexts of the BCL2 oncogene in mouse models impacts pre-malignant development

Follicular lymphoma (FL) is the most common indolent form of non-Hodgkin lymphoma arising from malignant germinal center (GC) B-cells. The genetic hallmark that leads to the development of FL is the t(14:18) which occurs early in the bone marrow during B cell development, thereby placing the anti-apoptotic BCL2 gene under the direct control of the transcriptional enhancers in 3 of immunoglobulin heavy chain locus (IgH 3RR) and leading to the constitutive expression of the BCL2 protein. To assess the impact of the BCL2 deregulation on B-cell fate and try to reproduce FL development in mice, two models were designed: the Ig{kappa}-BCL2 (Knock in of the BCL2 in the light chain Ig kappa locus) and the 3RR-BCL2 (Transgene containing BCL2 and a micro-3RR), both containing the full BCL2 promoter region.

immunology↗

bioRxiv2021

Nonclassical monocytes are prone to migrate into tumor in diffuse large B-cell lymphoma

Absolute count of circulating monocytes has been proposed as an independent prognostic factor in diffuse large B-cell lymphoma (DLBCL). However, monocyte nomenclature includes various subsets with pro-, anti-inflammatory, or suppressive functions, and their clinical relevance in DLBCL has been poorly explored. Herein, we broadly assessed circulating monocyte heterogeneity in 91 DLBCL patients. Classical- (cMO, CD14pos CD16neg) and intermediate- (iMO, CD14pos CD16pos) monocytes accumulated in DLBCL peripheral blood and exhibited an inflammatory phenotype. On the opposite, nonclassical monocytes (ncMO, CD14low CD16pos) were decreased in peripheral blood. Tumor-conditioned monocytes presented similarities with ncMO phenotype from DLBCL and were prone to migrate in response to CCL3, CCL5, and CXCL12, and presented similarities with DLBCL-infiltrated myeloid cells, as defined by mass cytometry. Finally, we demonstrated the adverse value of an accumulation of nonclassical monocytes in 2 independent cohorts of DLBCL. Key pointsO_LINonclassical monocytes are prone to migrate to DLBCL tumor C_LIO_LIHigh count of circulating nonclassical monocytes is an independent adverse event in DLBCL C_LI

immunology↗

bioRxiv2020

Stromal cells regulate malignant B-cell spatial organization, survival, and drug response in a new 3D model mimicking lymphoma tumor niche

Non-Hodgkin B-cell lymphomas (B-NHL) mainly develop within lymph nodes as densely packed aggregates of tumor cells and their surrounding microenvironment, creating a tumor niche specific to each lymphoma subtypes. Until now, in vitro preclinical models mimicking biomechanical forces, cellular microenvironment, and 3D organization of B lymphomas remain scarce while all these parameters constitute key determinants of lymphomagenesis and drug resistance. Using a microfluidic method based on the encapsulation of cells inside permeable, elastic, and hollow alginate microspheres, we developed a new tunable 3D-model incorporating extracellular matrix and/or stromal cells. Lymphoma B cells and stromal cells dynamically formed self-organized 3D spheroids, thus initiating a coevolution of these two cell types, reflecting their bidirectional crosstalk, and recapitulating the heterogeneity of B-NHL subtypes. In addition, this approach makes it suitable to assess in a relevant in vitro model the activity of new therapeutic agents in B-NHL.

cancer biology↗