ReviewClinical cancer research : an official journal of the American Association for Cancer Research2021
Siglec-15 as an Emerging Target for Next-generation Cancer Immunotherapy.
Review in Clinical cancer research : an official journal of the American Association for Cancer Research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 93 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
93 citing papers in PubMed, 1 synthesis or guideline pooled it, 140 citations in OpenAlex.
- Prognostic value of Siglec-15 expression in patients with solid tumors: A meta-analysis.Frontiers in oncology · 2022Pooled it
- Siglec-15 Expression in Gastric Carcinoma and Its Association With Clinicopathological Variables.World journal of oncology · 2026Article
- Persistent cytolytic CD8Cell reports. Medicine · 2026Article
- High SIGLEC10-Expressing Tumor-Associated Macrophages Participate in Remodeling the Tumor Immune Microenvironment and Predict Poor Prognosis in Colorectal Cancer.Cancer medicine · 2026Article
- Biosynthetic and genetic pathways related to sialic acid metabolism.The Journal of biological chemistry · 2026Review
- Sialic acids modulate immune responses in cancer: Therapeutic opportunities.The Journal of biological chemistry · 2026Review
- Mechanisms and intervention strategies of microenvironment-mediated drug resistance in multiple myeloma.Cancer cell international · 2026Review
- Molecular innate immune programs of tumor-associated macrophages in immune checkpoint blockade resistance: a staged framework from suppressive circuitry to translational bottlenecks.Frontiers in immunology · 2026Review
- Immunological and pathological roles of Siglecs: a molecular review.Frontiers in immunology · 2026Review
- Association between DPAGT1 and Siglec-15 expression and the malignant phenotype of hepatocellular carcinoma.American journal of cancer research · 2026Article
- Next-Generation Immune Checkpoints and Tumor Microenvironment Modulation in Cancer Immunotherapy.Journal of immunology research · 2026Review
- FXR shapes an immunosuppressive microenvironment in PD-L1lo/- non-small cell lung cancer by upregulating HVEM.JCI insight · 2025Article
- Glycomics in Human Diseases and Its Emerging Role in Biomarker Discovery.Biomedicines · 2025Review
- Unlocking new frontiers: novel immune targets for next-generation cancer immunotherapy.Korean journal of clinical oncology · 2025Review
- Anti-Tumor Activities of Anti-Siglec-15 Chimeric Heavy-Chain Antibodies.International journal of molecular sciences · 2025Article
- Siglec-15 antibody-GM-CSF chimera suppresses tumor progression via reprogramming tumor-associated macrophages.Journal for immunotherapy of cancer · 2025Article
- Expression feature and prognostic function of a novel immune checkpoint Siglec-15 in human colorectal cancer.Histology and histopathology · 2025Article
- Fusobacterium nucleatum-Derived Outer Membrane Vesicles Promote Immunotherapy Resistance via Changes in Tryptophan Metabolism in Tumour-Associated Macrophages.Journal of extracellular vesicles · 2025Article
- VSIG4Journal of experimental & clinical cancer research : CR · 2025Article
- Immune Cell Interactions and Immune Checkpoints in the Tumor Microenvironment of Gastric Cancer.International journal of molecular sciences · 2025Review
33 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
Immunomodulatory agents blocking the PD-1/PD-L1 pathway have shown a new way to treat cancer. The explanation underlying the success of these agents may be the selective expression of PD-L1 with dominant immune-suppressive activities in the tumor microenvironment (TME), supporting a more favorable tumor response-to-toxicity ratio. However, despite the big success of these drugs, most patients with cancer show primary or acquired resistance, calling for the identification of new immune modulators in the TME. Using a genome-scale T-cell activity array in combination with bioinformatic analysis of human cancer databases, we identified Siglec-15 as a critical immune suppressor with broad upregulation on various cancer types and a potential target for cancer immunotherapy. Siglec-15 has unique molecular features compared with many other known checkpoint inhibitory ligands. It shows prominent expression on macrophages and cancer cells and a mutually exclusive expression with PD-L1, suggesting that it may be a critical immune evasion mechanism in PD-L1-negative patients. Interestingly, Siglec-15 has also been identified as a key regulator for osteoclast differentiation and may have potential implications in bone disorders not limited to osteoporosis. Here, we provide an overview of Siglec-15 biology, its role in cancer immune regulation, the preliminary and encouraging clinical data related to the first-in-class Siglec-15 targeting mAb, as well as many unsolved questions in this pathway. As a new player in the cancer immunotherapeutic arena, Siglec-15 may represent a novel class of immune inhibitors with tumor-associated expression and divergent mechanisms of action to PD-L1, with potential implications in anti-PD-1/PD-L1-resistant patients.
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What OpenQuestion holds
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.