ArticleClinical cancer research : an official journal of the American Association for Cancer Research2023
Proinflammatory Macrophage Activation by the Polysialic Acid-Siglec-16 Axis Is Linked to Increased Survival of Patients with Glioblastoma.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 18 citations in OpenAlex.
- Sialylation in the nervous system: Functions and mechanisms.The Journal of biological chemistry · 2026Review
- Writers and readers of sialylation in immunoregulation in cancer.The Journal of biological chemistry · 2026Review
- Siglecs: From Biomodulation to Immunotherapy.Current protein & peptide science · 2026Review
- CAR-T Cell Therapy in Glioblastoma: Overcoming Immunological Barriers and Advancing Clinical Translation.Cancer management and research · 2026Review
- Regulatory T cells promote microglia-mediated synapse engulfment and functional recovery via the OPN-CD74 axis after spinal cord injury in mice.Journal of neuroinflammation · 2025Article
- Siglec-14-LGALS3BP glycoimmune axis shapes tumor-associated macrophage polarization and confers poor outcome in colorectal cancer.NPJ precision oncology · 2025Article
- Tumor-expressed GPNMB orchestrates Siglec-9Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Sialic acid metabolism-based classification reveals novel metabolic subtypes with distinct characteristics of tumor microenvironment and clinical outcomes in gastric cancer.Cancer cell international · 2025Article
- Human-specific elimination of epithelial Siglec-XII suppresses the risk of inflammation-driven colorectal cancers.JCI insight · 2024Article
- Targeting the MCP-GPX4/HMGB1 Axis for Effectively Triggering Immunogenic Ferroptosis in Pancreatic Ductal Adenocarcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Review
- Targeting the Siglec/sialic-acid axis in glioblastoma: Glycome-mediated immune evasion and emerging therapeutic platforms.Neuro-oncology advancesReview
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Authors and funding
22 authors at 3 institutions in 2 countries.
Funding
Abstract
purposeInteractions with tumor-associated microglia and macrophages (TAM) are critical for glioblastoma progression. Polysialic acid (polySia) is a tumor-associated glycan, but its frequency of occurrence and its prognostic value in glioblastoma are disputed. Through interactions with the opposing immune receptors Siglec-11 and Siglec-16, polySia is implicated in the regulation of microglia and macrophage activity. However, due to a nonfunctional SIGLEC16P allele, SIGLEC16 penetrance is less than 40%. Here, we explored possible consequences of SIGLEC16 status and tumor cell-associated polySia on glioblastoma outcome. EXPERIMENTAL
designFormalin-fixed paraffin-embedded specimens of two independent cohorts with 70 and 100 patients with newly diagnosed glioblastoma were retrospectively analyzed for SIGLEC16 and polySia status in relation to overall survival. Inflammatory TAM activation was assessed in tumors, in heterotypic tumor spheroids consisting of polySia-positive glioblastoma cells and Siglec-16-positive or Siglec-16-negative macrophages, and by exposing Siglec-16-positive or Siglec-16-negative macrophages to glioblastoma cell-derived membrane fractions.
resultsOverall survival of SIGLEC16 carriers with polySia-positive tumors was increased. Consistent with proinflammatory Siglec-16 signaling, levels of TAM positive for the M2 marker CD163 were reduced, whereas the M1 marker CD74 and TNF expression were increased, and CD8+ T cells enhanced in SIGLEC16/polySia double-positive tumors. Correspondingly, TNF production was elevated in heterotypic spheroid cultures with Siglec-16-expressing macrophages. Furthermore, a higher, mainly M1-like cytokine release and activating immune signaling was observed in SIGLEC16-positive as compared with SIGLEC16-negative macrophages confronted with glioblastoma cell-derived membranes.
conclusionsCollectively, these results strongly suggest that proinflammatory TAM activation causes the better outcome in patients with glioblastoma with a functional polySia-Siglec-16 axis.
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