SIGLEC15 expression

Consequently, SIGLEC15 correlates with tumor immune infiltration, molecular subtypes, and BRCA progression and prognosis. However, further research is required to elucidate the role of SIGLEC15 in breast cancer.

Siglec-15 was expressed in immunocytes such as macrophages in the peritumoral area, with a positive rate of 35.09%. Positive Siglec-15 expression in diffuse gliomas was correlated with smaller tumor size and higher ADC values.

Siglec-15 is a novel immunosuppressive protein expressed on tumor associated macrophages (TAMs) and tumor cells in many indications and is currently under clinical investigation (PYX-106, NCT05718557)...The co-expression of Siglec-15 and PD-L1 in tumors may inform indication selection for combination therapies. Future studies will expand this data set for NSCLC and evaluate other indications.

Collectively, the data suggested that Siglec-15 expression may serve as a novel prognostic factor and Siglec-15 might be identified as an ideal candidate for immunotherapy in CRC treatment.

The findings describe the metabolic landscape of HNSCC comprehensively and reveal that the Kyn/Siglec-15 axis may be a novel potential immunometabolism mechanism, providing a promising therapeutic strategy for cancers.

LUAD cases with up-regulated Siglec-15 expression, positive N status, and advance TNM stage suffered a critical unfavorable prognosis. In conclusion, Siglec-15 could be identified as a novel prognostic biomarker in LUAD and targeting Siglec-15 may provide a promising strategy for LUAD immunotherapy.

Siglec-15 enhanced cell invasion and proliferation, as we showed in vitro. Our study support Siglec-15 as a potential predictor for LSCC prognosis and an attractive target for LSCC immunotherapy.

In conclusion, PD-L1-independent Siglec-15 macrophages contribute to the formation of an immunosuppressive microenvironment in non-metastasis lung adenocarcinoma patients, which may cause a higher risk of recurrence. Siglec-15 could be a potential target for normalizing cancer immunotherapy, benefiting patients who fail to respond to anti-PD-L1 therapy.

With the highly concentrated glutathione (GSH) in the cytoplasm to destroy the nanostructure, the loaded IFNγ and siSiglec15 could be rapidly released, which could respectively repolarize macrophage phenotype to enhance CXCL9 secretion for T cell infiltration and silence Siglec15 expression to promote T cell proliferation, leading to significant inhibition of hepatocellular carcinoma (HCC) growth when combining with the immune checkpoint inhibitor. The strategy developed herein could be used as an effective tool to enhance cancer immunotherapy.

Among them, K145 CAR-T cells recognized and killed U87-MG and SK-OV-3 cell lines which express SIGLEC15, and were likely to proliferate well when compared to original CAR-T cells. Further analyses are needed, but these results suggest that SIGLEC15 might be an attractive target for new CAR-T-cell therapy, resulting in advancement of the treatment for solid and liquid tumors.

We obtained similar results with immune-resistant SB28 model. This work suggests that oncolytic therapy combined with blocking myeloid checkpoint Siglec-15, using an agent already in humans, and blocking CD8+ T cell checkpoint with anti-PD1, is worthy of study in humans.

Knockdown of Sig-15 in A20 cells abrogates disease progression in WT but not immune deficient mice (Log-rank, **p <0.0001, n=10 mice/group), consistent with a role for Sig-15 in immune evasion in lymphoma (Figure 1B). Together, these data implicate Sig-15 as an immune checkpoint that may be inhibited therapeutically to promote an immune response to lymphoma cells.