ArticleProceedings of the National Academy of Sciences of the United States of America2014
Engagement of myelomonocytic Siglecs by tumor-associated ligands modulates the innate immune response to cancer.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 141 papers.
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Who cites it
141 citing papers in PubMed, 226 citations in OpenAlex.
- Antibody-lectin chimeras for glyco-immune checkpoint blockade.Nature biotechnology · 2026Article
- Sialic acid-modified phosphorene for low-necrosis and targeted drug delivery in breast cancer.RSC advances · 2026Article
- Roles of neutrophil extracellular traps in cancer immunotherapy resistance and therapeutic targeting.Biomarker research · 2026Review
- Sialylation in Colorectal Cancer Rewires Antitumor Immunity at the Peritoneal Metastatic Site.European journal of immunology · 2026Article
- Siglec-14-LGALS3BP glycoimmune axis shapes tumor-associated macrophage polarization and confers poor outcome in colorectal cancer.NPJ precision oncology · 2025Article
- HIV-induced sialoglycans on infected CD4+ T cells promote immune evasion from myeloid cell-mediated killing.Nature communications · 2025Article
- Molecular Insights into the Engagement of High-Affinity Sialylated Ligands to Human CD22.JACS Au · 2025Article
- Targeting Myeloid Cells for Cancer Immunotherapy.Cancer immunology research · 2025Review
- Increase of Inhibitory Siglec receptors on T cells mitigates severe immune reactions during acute viral infections.PNAS nexus · 2025Article
- Decoding SIGLEC12 in Bladder Cancer: In Silico Profiling of Expression, Tumor-Immune Interactions, and Prognostic Impact.Medicina (Kaunas, Lithuania) · 2025Article
- Dysregulated Sialylation in Cancer: From Immunosuppressive Microenvironment to Siglec-Targeted Therapeutics.Biomolecules · 2025Review
- Tumor-expressed GPNMB orchestrates Siglec-9Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Surfaceome: a new era in the discovery of immune evasion mechanisms of circulating tumor cells.Molecular oncology · 2025Review
- Tumor glyco-immunology, glyco-immune checkpoints and immunotherapy.Journal for immunotherapy of cancer · 2025Review
- IL-4-STAT6-induced high Siglec-G/10 expression aggravates the severe immune suppressive tumor microenvironment and impedes the efficacy of immunotherapy in head and neck squamous cell carcinoma.Journal for immunotherapy of cancer · 2025Article
- The inhibitory receptor Siglec-E controls antigen-presenting cell activation and T cell-mediated transplant rejection.Science translational medicine · 2025Article
- Insights on the Role of Sialic Acids in Acute Lymphoblastic Leukemia in Children.International journal of molecular sciences · 2025Review
- Proximity Labeling and Genetic Screening Reveal that DSG2 is a Counter Receptor of Siglec-9 and Suppresses Macrophage Phagocytosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Targeting Siglec-E facilitates tumor vaccine-induced antitumor immunity in renal carcinoma.Journal for immunotherapy of cancer · 2025Article
- Targeting immune checkpoints on myeloid cells: current status and future directions.Cancer immunology, immunotherapy : CII · 2025Review
81 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
Certain pathogenic bacteria are known to modulate the innate immune response by decorating themselves with sialic acids, which can engage the myelomonocytic lineage inhibitory receptor Siglec-9, thereby evading immunosurveillance. We hypothesized that the well-known up-regulation of sialoglycoconjugates by tumors might similarly modulate interactions with innate immune cells. Supporting this hypothesis, Siglec-9-expressing myelomonocytic cells found in human tumor samples were accompanied by a strong up-regulation of Siglec-9 ligands. Blockade of Siglec-9 enhanced neutrophil activity against tumor cells in vitro. To investigate the function of inhibitory myelomonocytic Siglecs in vivo we studied mouse Siglec-E, the murine functional equivalent of Siglec-9. Siglec-E-deficient mice showed increased in vivo killing of tumor cells, and this effect was reversed by transgenic Siglec-9 expression in myelomonocytic cells. Siglec-E-deficient mice also showed enhanced immunosurveillance of autologous tumors. However, once tumors were established, they grew faster in Siglec-E-deficient mice. In keeping with this, Siglec-E-deficient macrophages showed a propensity toward a tumor-promoting M2 polarization, indicating a secondary role of CD33-related Siglecs in limiting cancer-promoting inflammation and tumor growth. Thus, we define a previously unidentified impact of inhibitory myelomonocytic Siglecs in cancer biology, with distinct roles that reflect the dual function of myelomonocytic cells in cancer progression. In keeping with this, a human polymorphism that reduced Siglec-9 binding to carcinomas was associated with improved early survival in non-small-cell lung cancer patients, which suggests that Siglec-9 might be therapeutically targeted within the right time frame and stage of disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.