ArticleLaboratory investigation; a journal of technical methods and pathology2022
Development of an immunohistochemical assay for Siglec-15.
Article in Laboratory investigation; a journal of technical methods and pathology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.
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Who cites it
8 citing papers in PubMed, 1 synthesis or guideline pooled it, 13 citations in OpenAlex.
- Prognostic value of Siglec-15 expression in patients with solid tumors: A meta-analysis.Frontiers in oncology · 2022Pooled it
- Immune Cell Interactions and Immune Checkpoints in the Tumor Microenvironment of Gastric Cancer.International journal of molecular sciences · 2025Review
- Siglec15/TGF-β bispecific antibody mediates synergistic anti-tumor response against 4T1 triple negative breast cancer in mice.Bioengineering & translational medicine · 2024Article
- The Potential of Siglecs and Sialic Acids as Biomarkers and Therapeutic Targets in Tumor Immunotherapy.Cancers · 2024Review
- Novel Siglec-15-Sia axis inhibitor leads to colorectal cancer cell death by targeting miR-6715b-3p and oncogenes.Frontiers in immunology · 2023Article
- Siglec15 is a prognostic indicator and a potential tumor-related macrophage regulator that is involved in the suppressive immunomicroenvironment in gliomas.Frontiers in immunology · 2023Article
- Quantitative assessment of Siglec-15 expression in lung, breast, head, and neck squamous cell carcinoma and bladder cancer.Laboratory investigation; a journal of technical methods and pathology · 2022Article
- Unveiling the molecular features, relevant immune and clinical characteristics ofFrontiers in immunology · 2022Article
Corrections and comments
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Authors and funding
18 authors at 3 institutions in 3 countries.
Funding
Abstract
Siglec-15, a member of sialic-acid binding immunoglobulin type lectins, is normally expressed by myeloid cells and upregulated in some human cancers and represents a promising new target for immunotherapy. While PD-L1 blockade is an important strategy for immunotherapy, its effectiveness is limited. The expression of Siglec-15 has been demonstrated to be predominantly mutually exclusive to PD-L1 in certain cancer histologies. Thus, there is significant opportunity for Siglec-15 as an immunotherapeutic target for patients that do not respond to PD-1/PD-L1 inhibition. The aim of this study was to prospectively develop an immunohistochemical (IHC) assay for Siglec-15 to be used as a companion diagnostic for future clinical trials. Here, we create and validate an IHC assay with a novel recombinant antibody to the cytoplasmic domain of Siglec-15. To find an enriched target, this antibody was first used in a quantitative fluorescence (QIF) assay to screen a broad range of tumor histologies to determine tumor types where Siglec-15 demonstrated high expression. Based on this and previous data, we focused on development of a chromogenic IHC assay for lung cancer. Then we developed a scoring system for this assay that has high concordance amongst pathologist readers. We then use this chromogenic IHC assay to test the expression of Siglec-15 in two cohorts of NSCLC. We found that this assay shows a higher level of staining in both tumor and immune cells compared to previous QIF assays utilizing a polyclonal antibody. However, similar to that study, only a small percentage of positive Siglec-15 cases showed high expression for PD-L1. This validated assay for Siglec-15 expression may support development of a companion diagnostic assay to enrich for patients expressing the Siglec-15 target for therapy.
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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.