Siglecs, Novel Immunotherapy Targets, Potentially Enhance The Effectiveness of Existing Immune Checkpoint Inhibitors in Glioma Immunotherapy

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Abstract
Background: Inhibitors of immune checkpoints have shown little effect in clinical trials involving glioma patients. Here, we explored novel targets for use in future treatments. Previous studies showed the sialic acid-binding Ig-like lectin (Siglec) family to have a specific role in immunosuppression. We aimed to study the characteristics and immune function of Siglec family members. Methods: Transcriptome data from 1024 glioma samples and 1551 glioma single cells were used in our study. Clinical and molecular pathology information was also included. Statistical, bioinformatical methods, and single-cell sequencing analysis were applied to investigate the role of Siglec family members. Results: Siglecs-5, −7, −9, and −16 showed a significant correlation with immunosuppression in glioma. They are typically expressed in higher grade, IDH-wildtype, and mesenchymal subtype gliomas. Siglec-5, −7, and −9 had a similar immune function to TIM-3, while Siglec-16 was similar to PD-L1, suppressing tumor immunity via different mechanisms. Joint use of Siglec-inhibitors and immune checkpoint inhibitors could prolong the survival of glioma patients. Conclusion: Siglec-5, −7, −9, and −16 suppressed tumor immunity in different ways. Joint usage of inhibitors may be an effective means to improve the efficacy of glioma immunotherapy.

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