Biology subjects

Chiodin, G.

Publications and source records attributed to Chiodin, G..

3 recordsLinked to original sources

bioRxiv2025

DC-SIGN Binding to the Surface Ig Oligomannose-type Glycans Promotes Follicular Lymphoma Cell Adhesion and Survival

The occupation of the surface immunoglobulin antigen-binding site by oligomannose-type glycans (sIg-Mann) is a tumor-specific post-translational modification of classic follicular lymphoma (FL). SIg-Mann switches binding from antigen to dendritic cell-specific intercellular adhesion molecule 3 grabbing non-integrin (DC-SIGN), known to be expressed on interfollicular macrophages and FL-associated follicular dendritic cells (FDCs). The interaction with DC-SIGN induces reorganization of sIg-Mann in wider and less dense clusters than anti-Ig, consistent with inefficient DC-SIGN-induced endocytosis and a low-level intracellular signaling. However, ligand-specific cell clusters form between sIg-Mann-expressing lymphoma and DC-SIGN-expressing cells, raising a need to understand the functional consequences of the interaction of DC-SIGN with sIg-Mann on primary FL cells. This engagement induces adhesion of FL cells to VCAM-1 via B-cell receptor proximal kinases and actin regulators in a fashion similar to anti-Ig, but without initiating apoptosis in vitro. Instead, antibody blockade of sIg-Mann contact with DC-SIGN expressed on FDC-derived YK6/SIGN cells inhibits adhesion and survival of primary FL cells in vitro. These data highlight that the specific interaction with DC-SIGN induces FL cell adhesion to VCAM-1, likely allowing FL cell retention in the lymph node, and survival of the FL cells. Adhesion and survival are inhibited by an anti-DC-SIGN blocking antibody, indicating a new early therapeutic approach against FL retention and survival in adaptive tumor tissue niches. Key pointsO_LIDC-SIGN promotes FL cell adhesion to VCAM-1 via B-cell receptor proximal kinases and actin regulators C_LIO_LIDC-SIGN interaction with sIg-Mann sustains the survival of FL cells C_LI

cancer biology↗

bioRxiv2025

The Origin, Diagnosis, and Prognosis of Oligomannose-Type Diffuse Large B Cell Lymphoma

The acquisition of N-glycosylation sites occupied by oligomannose-type glycans in the immunoglobulin complementarity-determining region (CDR) is an early clonal tumor-specific identifier of follicular lymphoma (FL). CDR-located N-glycosylation sites are also acquired in germinal-center-B-cell-like diffuse large B-cell lymphomas (GCB-DLBCL), but their significance is less defined. We used RNA-seq immunoglobulin assembly to determine the frequency and CDR location of the acquired N-glycosylation sites (AGS) in two large independent DLBCL cohorts. Composition of the glycans occupying the AGS was determined using liquid chromatography-mass spectrometry and correlated with cell-of-origin, FL signature (defined by EZB phenotype or BCL2 translocation), transcript profile, and clinical outcome. CDR-located AGS were observed in 41-46% of GCB-DLBCL but were rare in other DLBCL. Only CDR-located AGS of DLBCL with an FL signature were occupied by oligomannose-type glycans. These DLBCL were termed Mann-type DLBCL. Conversely, the AGS of the other DLBCL were either non-glycosylated or occupied by complex-type glycans. Mann-type status was an independent marker of short progression-free survival and overall survival. In contrast, the other GCB-DLBCL cases, including those with an FL signature but without AGS, had the best outcomes. Mann-type DLBCL overexpressed gene-sets of cell growth, survival, and cycling, and underexpressed proinflammatory and apoptotic pathways, irrespective of concomitant MYC translocations. Acquisition of Mann-type glycans is a highly selective environmental pressure, identifying the most aggressive GCB-DLBCL with an origin related to FL. The detection of AGS in the CDR of GCB-DLBCLs with a BCL2 translocation defines Mann-type DLBCLs, refines prognosis and marks a precise tumor interaction to block early therapeutically. Key pointsO_LIAcquisition of Mann-type glycans is a tumor-specific environmental pressure identifying the most aggressive GCB-DLBCL with an origin related to FL. C_LIO_LIMann-type DLBCL can be diagnosed by the concomitant detection of AGS in the CDR and a BCL2 translocation. C_LI

cancer biology↗

bioRxiv2024

IgSeqR: a protocol for the identification, assembly, and characterization of full-length tumor Immunoglobulin transcripts from unselected RNA sequencing data

Immunoglobulin (IG) gene analysis provides fundamental insight into B-cell receptor structure and function. In B-cell tumors, it can inform the cell of origin and clinical outcomes. Its clinical value has been established in the two types of chronic lymphocytic leukemia with unmutated or mutated IGHV genes and is emerging in other B-cell tumors. The traditional PCR-based techniques, which are labor-intensive, rely on the attainment of either a dominant sequence or a small number of subclonal sequences and do not allow automated matching with the clonal phenotypic features. Extraction of the expressed tumor IG transcripts using high-throughput RNA sequencing (RNA-seq) can be faster and allow the collection of multiple sequences matched with the transcriptome profile. Analytical tools are regularly sought to increase the accuracy, depth, and speed of acquisition of the full IGV-(IGD)-IGJ-IGC sequences and combine the IG characteristics with other RNA-seq data. We provide here a user-friendly protocol for the rapid extraction, identification, and accurate determination of the full (leader to constant region) tumor IG templated and non-templated transcript sequence from RNA-seq. The derived amino acid sequences can be interrogated for their physico-chemical characteristics and, in certain lymphomas, predict tumor glycan types occupying acquired N-glycosylation sites. These features will then be available for association studies with the tumor transcriptome. The resulting information can also help refine diagnosis, prognosis, and potential therapeutic targeting in the most common lymphomas.

bioinformatics↗