Abstract A014: OR2B6 is a chemosensor associated with activated B-cell like diffuse large B cell and mantle cell lymphoma
Giulio Sartori, Sara Sabatini, Alessandro Ghiringhelli, Natalie Amberg, Luciano Cascione, Jacopo Sgrignani, Hiroaki Matsunami, Andrea Cavalli, Francesco BertoniAbstract
Background.
Olfactory receptors (ORs) are a large subgroup of chemosensors within the G protein-coupled receptor (GPCR) family and have been found ectopically throughout the human body, where they fulfil a range of functions and are associated with the pathogenesis of numerous diseases. While certain ORs have been linked to cancer development, evidence regarding their role in hematological diseases remains scarce. OR13A1 is part of the double-hit expression signature (HGBL-DH/TH) in diffuse large B-cell lymphoma (DLBCL) (Ennishi et al. 2019), is more expressed in germinal center B-cell (GCB) DLBCL where it sustains lymphoma cells’ growth (Sartori et al, 2022). Here, we quantified the ORs expression in lymphoma clinical specimens and performed functional experiments in cell lines.
Methods.
Gene expression data for clinical samples were obtained from the public dataset phs001444.v2.p1. Patients were stratified according to OR expression groups. Kaplan–Meier survival analysis was performed to evaluate differences in outcome between groups, and LIMMA was used to identify OR-associated gene expression signatures. OR’s expression was first evaluated using a previously generated total RNA-Seq dataset from 47 B-cell lymphoma cell lines and then was assessed by qPCR across five human cell lines: two GCB-DLBCL (OCI-Ly7 and VAL), two activated B-cell-like (ABC)-DLBCL (U2932 and HBL1), and one mantle cell lymphoma (MCL) (JEKO1). OR2B6 silencing was performed in HBL1 and JEKO1 cells using doxycycline-inducible shRNAs, and viability was monitored via live imaging.
Results.
OR13A1, OR2B6, and OR51E2 were expressed in at least 50% of patients, but only OR13A1 and OR2B6 were detected in RNASeq data from lymphoma cell lines. The lack of OR51E2 in cell lines was suggestive of its expression by cells of the tumor microenvironment (TME), such as macrophages, as recently reported in prostate cancer (Marelli et al, 2025). As expected, OR13A1 was associated with HGBL (DH/TH)-related genes and germinal center B cell-like signatures. OR2B6 was associated with ABC-DLBCL genes and down-regulated HGBL (DH/TH) genes. By qPCR OR13A1 was predominantly expressed in GCB-DLBCL (2-ΔCt = 0.015), moderately in MCL (2-ΔCt = 0.007) and almost absent in ABC-DLBCL (2-ΔCt < 0.0004). In contrast, OR2B6 was mostly expressed in ABC-DLBCL (2-ΔCt = 0.004) and MCL (2-ΔCt = 0.002), with negligible expression in GCB-DLBCL (2-ΔCt < 0.0004). While OR13A1 had already been identified in our lab as an essential gene in GCB-DLBCL, OR2B6 was validated as essential in HBL1 and JEKO1 cell lines derived from ABC and MCL, respectively.
Conclusion.
These findings suggest that three chemosensors from the OR family may play a role in lymphoma development: OR13A1 (GCB-DLBCL), OR2B6 (ABC-DLBCL and MCL), expressed by lymphoma cells, and OR51E2, expressed by the TME. Further research is needed to identify their ligands, understand their biological mechanisms, and evaluate their therapeutic potential.
Citation Format:
Giulio Sartori, Sara Sabatini, Alessandro Ghiringhelli, Natalie Amberg, Luciano Cascione, Jacopo Sgrignani, Hiroaki Matsunami, Andrea Cavalli, Francesco Bertoni. OR2B6 is a chemosensor associated with activated B-cell like diffuse large B cell and mantle cell lymphoma [abstract]. In: Proceedings of the Fifth AACR International Meeting on Advances in Malignant Lymphoma: From Discovery to Clinical Impact; 2026 Jun 24-27; Philadelphia, PA. Philadelphia (PA): AACR; Blood Cancer Discov 2026;7(3_Suppl):Abstract nr A014.