SIGLEC8 (Sialic Acid Binding Ig Like Lectin 8)

Our review underscores the potential of targeting EOS-specific receptors, including IL-5Rα and Siglec-8, for therapeutic interventions in EOS-related diseases. By combining recent findings on the metabolic milieu and interactions of EOS within complex tissue environments, we provide a comprehensive perspective on their physiological and pathological functions, paving the way for novel therapeutic strategies.

High SIGLEC8 expression predicts longer survival in SKCM. We propose that SIGLEC8 boosts antitumor immunity by influencing B‑cell and T‑cell pathways (including FCER2, CR2, MS4A1, and CD8A/B) in the tumor microenvironment. SIGLEC8 thus shows promise as a low‑cost prognostic biomarker and a potential therapeutic target. Table S1 shows cancer-type-specific prognostic effects for SIGLEC8: in SKCM higher SIGLEC8 expression associates with improved survival, whereas prognostic directionality varies across other tumor types. A pan-cancer comparison revealed cancer-type-specific prognostic effects for SIGLEC8: in SKCM higher SIGLEC8 expression associates with improved survival, whereas prognostic directionality varies across other tumor types.

Spatial sequencing of kidney biopsies, especially from patients with high disease activity, uncovered similar neutrophils in intrarenal inflammatory niches, and their abundance was lower after repetitive low-dose glucocorticoid application. These findings identify proinflammatory neutrophils as progression drivers in cGN and suggest that low-dose glucocorticoid therapy may be sufficient to suppress them.

For the prognosis of patients with LGG, the transcriptional activity of SIGLEC8 is increased in LGG tissues and is an independent risk factor. Interference with SIGLEC8 could promote tumor progression by regulating the JAK/STAT signaling pathway, indicating that SIGLEC8 may function as a distinctive predictive biomarker for patients with LGG.

P=N/A, N=100, Not yet recruiting, Centre Hospitalier Universitaire de Besancon

Here, we present the 10-year follow-up of a heavily pre-treated patient with several lines of therapy, achieving a remarkable complete response to anti-PD-1 rechallenge. In addition, we highlight a common immune-related adverse event of anti-PD-1, eosinophilia, as a possible biomarker of response and using TCGA data analysis, provide proof-of-concept for tumor expression of the eosinophil-related gene SIGLEC8, as a promising powerful predictor of prognosis for papillary renal cell carcinoma patients.

A novel flow cytometric antibody panel was devised to detect alterations in immunophenotypic patterns of bone marrow eosinophil maturation and evaluated in normal, HES and SM samples. This approach will allow us to elucidate changes in immunophenotypic patterns of bone marrow eosinophilopoiesis in other hematological diseases.

Avapritinib and midostaurin can also temper IgE-mediated degranulation...Recently, the anti Siglec-8 antibody lirentelimab showed promising results in ISM...Long-term safety of TKI needs to be addressed. New drugs under investigation in diseases in which non-neoplastic MCs play a pivotal role can provide important inputs to identify new efficient and safe treatments for MCAS.

Compared to remaining blood neutrophils, CD79b neutrophils are primed for NETosis, express higher levels of antigen presentation-related proteins, and have an increased capacity for phagocytosis. Our work suggests that CD79b neutrophils are associated with early-stage melanoma.

Likewise, KHYG-1 cells transduced with a Siglec-8C2-set CAR generated from 2A3 or 2F10 induced significant cytotoxicity against EOL-1 and RS4; 11 cells transduced with Siglec-8FL as well as against Siglec-8-enriched HMC 1.2 cells, albeit to a very modest extent. Together, our data demonstrate Siglec-8-directed immunotherapies can be highly potent, even against target cells expressing very limited copy numbers of Siglec-8 molecules, supporting their further development for use in patients with difficult-to-treat eosinophilic and mast cell disorders.