ArticleBlood advances2022
Targeting hypersialylation in multiple myeloma represents a novel approach to enhance NK cell-mediated tumor responses.
Article in Blood advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 81 citations in OpenAlex.
- Antibody-lectin chimeras for glyco-immune checkpoint blockade.Nature biotechnology · 2026Article
- Surfaceome CRISPR activation screening uncovers ligands regulating tumor sensitivity to NK cell killing.Nature communications · 2026Article
- Immune implications and therapeutic opportunities of tumor glycosylation.Nature cancer · 2026Review
- Sialic Acids in Kidney Disease: Immune Regulation, Complement Activation and Glomerular Injury.Antioxidants (Basel, Switzerland) · 2026Review
- Sialylation in Colorectal Cancer Rewires Antitumor Immunity at the Peritoneal Metastatic Site.European journal of immunology · 2026Article
- Aberrant glycosylation in hematologic malignancies: mechanisms, immune evasion, and therapeutic targeting.Blood cancer journal · 2026Review
- CRISPR activation screens map the genomic landscape of cancer glycome remodeling.Cell genomics · 2026Article
- Article
- Writers and readers of sialylation in immunoregulation in cancer.The Journal of biological chemistry · 2026Review
- Enhanced sialylation of bone marrow mesenchymal stromal cells contributes to immune remodeling through macrophage polarization in multiple myeloma patients.Frontiers in immunology · 2026Article
- Dual Regulation of Post-Translational Modification of Proteins: Bottlenecks and Breakthroughs in NK Cell Therapy for Glioblastoma.International journal of general medicine · 2026Review
- HIV-induced sialoglycans on infected CD4+ T cells promote immune evasion from myeloid cell-mediated killing.Nature communications · 2025Article
- CAR-NK cell therapy in multiple myeloma: from preclinical and clinical landscape to joining the force for treatment strategies optimization.Cell communication and signaling : CCS · 2025Review
- Decoding SIGLEC12 in Bladder Cancer: In Silico Profiling of Expression, Tumor-Immune Interactions, and Prognostic Impact.Medicina (Kaunas, Lithuania) · 2025Article
- Stromal cells modulate innate immune cell phenotype and function in colorectal cancer via the Sialic acid/Siglec axis.Journal for immunotherapy of cancer · 2025Article
- Targeting Siglec-sialic acid checkpoint to reverse immune dysfunction mediated by plasmacytoid dendritic cells in myeloma.Blood advances · 2025Article
- Dysregulated Sialylation in Cancer: From Immunosuppressive Microenvironment to Siglec-Targeted Therapeutics.Biomolecules · 2025Review
- Membrane-Inserting α‑Lipid Polymers: Understanding Lipid Membrane Insertion and Effect on Membrane Fluidity.Chemistry of materials : a publication of the American Chemical Society · 2025Article
- Integrated in vivo functional screens and multiomics analyses identify α-2,3-sialylation as essential for melanoma maintenance.Science advances · 2025Article
- The Tumour Glyco-Code: Sialylation as a Mediator of Stromal Cell Immunosuppression in the Tumour Microenvironment.European journal of immunology · 2025Review
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
Abstract
Abnormal glycosylation is a hallmark of cancer, and the hypersialylated tumor cell surface facilitates abnormal cell trafficking and drug resistance in several malignancies, including multiple myeloma (MM). Furthermore, hypersialylation has also been implicated in facilitating evasion of natural killer (NK) cell-mediated immunosurveillance but not in MM to date. In this study, we explore the role of hypersialylation in promoting escape from NK cells. We document strong expression of sialic acid-derived ligands for Siglec-7 (Siglec-7L) on primary MM cells and MM cell lines, highlighting the possibility of Siglec-7/Siglec-7L interactions in the tumor microenvironment. Interactomics experiments in MM cell lysates revealed PSGL-1 as the predominant Siglec-7L in MM. We show that desialylation, using both a sialidase and sialyltransferase inhibitor (SIA), strongly enhances NK cell-mediated cytotoxicity against MM cells. Furthermore, MM cell desialylation results in increased detection of CD38, a well-validated target in MM. Desialylation enhanced NK cell cytotoxicity against CD38+ MM cells after treatment with the anti-CD38 monoclonal antibody daratumumab. Additionally, we show that MM cells with low CD38 expression can be treated with all trans-retinoic acid (ATRA), SIA and daratumumab to elicit a potent NK cell cytotoxic response. Finally, we demonstrate that Siglec-7KO potentiates NK cell cytotoxicity against Siglec-7L+ MM cells. Taken together, our work shows that desialylation of MM cells is a promising novel approach to enhance NK cell efficacy against MM, which can be combined with frontline therapies to elicit a potent anti-MM response.
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