Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Waldenstrom's Macroglobulinemia (WM) is an IgM-secreting bone marrow (BM) lymphoma that is preceded by an asymptomatic state (AWM). To dissect tumor-intrinsic and immune mechanisms of progression, we perform single-cell RNA-sequencing on 294,206 BM tumor and immune cells from 30 patients with AWM/WM, 26 patients with Smoldering Myeloma, and 23 healthy donors. Despite their early stage, patients with AWM present extensive immune dysregulation, including in normal B cells, with disease-specific immune hallmarks. Patient T and NK cells show systemic hypo-responsiveness to interferon, which improves with interferon administration and may represent a therapeutic vulnerability. MYD88-mutant tumors show transcriptional heterogeneity, which can be distilled in a molecular classification, including a DUSP22/CD9-positive subtype, and progression signatures which differentiate IgM MGUS from overt WM and can help advance WM research and clinical practice.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11811135 | PMC |
| http://dx.doi.org/10.1038/s41467-025-56323-w | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Comparative efficacy of Naringenin and Sinomenine in facilitating the differentiation of mouse hematopoietic stem cells into immature dendritic cells to promote transplantation immunological regulation.
Transpl Immunol
September 2025
Department of Kidney Transplantation, Hospital of Nephropathy, The First Affiliated Hospital of Medical College of Xi'an Jiaotong University, China.
Objective: Immature dendritic cells (imDC) are crucial in facilitating transplant immunological regulation. However, imDC is readily amenable to maturation. Sinomenine (Sin) naringin (Nar) are traditional Chinese medicine with immunoregulation and anti-inflammatory activities.
View Article and Find Full Text PDFSingle-cell RNA sequencing defines distinct disease subtypes and reveals hypo-responsiveness to interferon in asymptomatic Waldenstrom's Macroglobulinemia.
Nat Commun
February 2025
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Waldenstrom's Macroglobulinemia (WM) is an IgM-secreting bone marrow (BM) lymphoma that is preceded by an asymptomatic state (AWM). To dissect tumor-intrinsic and immune mechanisms of progression, we perform single-cell RNA-sequencing on 294,206 BM tumor and immune cells from 30 patients with AWM/WM, 26 patients with Smoldering Myeloma, and 23 healthy donors. Despite their early stage, patients with AWM present extensive immune dysregulation, including in normal B cells, with disease-specific immune hallmarks.
View Article and Find Full Text PDFBorrelia burgdorferi initiates early transcriptional re-programming in macrophages that supports long-term suppression of inflammation.
PLoS Pathog
December 2023
Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts, United States of America.
Borrelia burgdorferi (Bb), the causative agent of Lyme disease, establishes a long-term infection and leads to disease manifestations that are the result of host immune responses to the pathogen. Inflammatory manifestations resolve spontaneously despite continued bacterial presence, suggesting inflammatory cells become less responsive over time. This is mimicked by in vitro repeated stimulations, resulting in tolerance, a phenotypic subset of innate immune memory.
View Article and Find Full Text PDFOral administration of ovalbumin protects mice from concanavalin A-induced hepatitis through suppression of interferon-gamma responses.
Biochem Biophys Res Commun
September 2023
Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka, 589-8511, Japan.
The liver is a tolerogenic organ that exhibits hypo-responsiveness to antigens circulating in the portal vein. Antigens that are orally administered at high doses reach the liver. In our previous study, we demonstrated that administering ovalbumin (OVA) orally at high doses generates unique CD4 T cells and tolerogenic dendritic cells, both of which can suppress T helper type 1 (Th1) responses, in the livers of two groups of mice: DO11.
View Article and Find Full Text PDFPropionate induces cross-tolerance to TLR1/2 and TLR4 agonists in an IFIT-dependent manner.
Immunobiology
March 2022
Leibniz Institute of Immunotherapy (LIT); Chair for Immunology, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany. Electronic address:
In this study, we have identified Interferon-stimulated genes (ISGs), especially IFIT1, 2 and 3, as target genes of propionate-induced signalling in the human epithelial cell line A549, the monocytic cell line THP-1 as well as in primary, human peripheral blood-derived macrophages (PBMs). Induction of the IFIT gene family by propionate negatively regulates TLR-induced signalling. Propionate stimulation results in downregulation of pro-inflammatory cytokine and chemokine expression as well as MHC class II expression upon TLR1/2 and TLR4 re-stimulation in A549 and THP-1 cells as well as in PBMs, demonstrating that propionate-induced signalling is involved in the induction of TLR cross-tolerance.
View Article and Find Full Text PDF