ArticleProceedings of the National Academy of Sciences of the United States of America2021
Siglecs-7/9 function as inhibitory immune checkpoints in vivo and can be targeted to enhance therapeutic antitumor immunity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.
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Who cites it
105 citing papers in PubMed, 164 citations in OpenAlex.
- Sialic acidOncoimmunology · 2026Article
- Antibody-lectin chimeras for glyco-immune checkpoint blockade.Nature biotechnology · 2026Article
- Targeting glycans for cancer immunotherapy.Nature biotechnology · 2026Article
- Siglec-7 orchestrates mitochondrial dynamics and metabolic reprogramming to restrain human NK cell cytotoxic function.The Journal of biological chemistry · 2026Article
- Pathophysiological roles of monocytes and macrophages in cancer.Nature reviews. Immunology · 2026Review
- Immune implications and therapeutic opportunities of tumor glycosylation.Nature cancer · 2026Review
- Protocol for assessing anti-Siglec-9 antibody-mediated tumor phagocytosis by macrophages using pH-sensitive dyes and flow cytometry.STAR protocols · 2026Article
- Sialylation profile and Siglec-E expression across tissues in the B16OVA melanoma mouse model.Glycobiology · 2026Article
- Targeting Siglec-E Modulates Macrophage Polarization to Attenuate Cardiac Remodeling After Myocardial Infarction.Journal of cardiovascular translational research · 2026Article
- Single-Cell Atlas of Renal Cell Carcinoma Brain Metastasis Uncovers Mechanisms of Immune Dysfunction and Resistance.bioRxiv : the preprint server for biology · 2026Article
- Targeting ST3GAL1 to downregulate ligands for the glycoimmune checkpoint Siglec-7 and reverse immune escape in hepatocellular carcinoma.Cancer immunology, immunotherapy : CII · 2026Article
- Sialic acids modulate immune responses in cancer: Therapeutic opportunities.The Journal of biological chemistry · 2026Review
- Innovative immunotherapy approaches: harnessing synergy of dual checkpoint blockade in oncology.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Defective HLA-G1 glycosylation disrupts Siglec-7-mediated NK cell tolerance at the maternal-fetal interface in recurrent pregnancy loss.Cell communication and signaling : CCS · 2026Article
- Article
- Deciphering the role of glycolipids as emerging therapeutic targets in EMT-driven cancer progression.Discover oncology · 2026Review
- Sweet Surprises: Decoding Tumor-Associated Glycosylation in Cancer Progression and Therapeutic Potential.Cells · 2026Review
- Glycan-encoded immune checkpoints and allorecognition: a mechanistic framework for transplantation and organ engineering.Frontiers in transplantation · 2026Review
- Siglec-7 inhibits TLR3-induced pro-inflammatory cytokine production from human monocytes and macrophages.Frontiers in immunology · 2026Article
- The role of SIGLEC9 in immunosuppression and prognosis in cervical cancer.Clinics (Sao Paulo, Brazil) · 2025Article
45 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Given the role of myeloid cells in T cell activation and in the antitumor response, targeting checkpoint molecules expressed on this population represents a promising strategy to augment antitumor immunity. However, myeloid checkpoints that can be effectively used as immunotherapy targets are still lacking. Here, we demonstrate the therapeutic potential of targeting the myeloid receptors Siglec-7 and Siglec-9 in vivo. By using a humanized immunocompetent murine model, we demonstrate that human Siglec-7 and Siglec-9, in addition to the murine homolog Siglec-E, inhibit the endogenous antitumor immune response, as well as the response to tumor-targeting and immune checkpoint inhibiting antibodies in vivo. The impact of these Siglecs on tumor progression is highly dependent on the anatomical distribution of the tumor and, as a consequence, the local tumor microenvironment, as tumors with a more immune-suppressive tumor microenvironment are less sensitive to Siglec perturbation. Finally, to assess the potential of these two receptors as targets for immunotherapy, we developed Fc engineered blocking antibodies to Siglec-7 and Siglec-9 and demonstrate that Siglec-7 and Siglec-9 blockade can significantly reduce tumor burden in vivo, demonstrating the therapeutic potential of targeting these two receptors.
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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.