# ASGR2 and CLEC12A as Prognostically Relevant C-Type Lectin Hubs in Glioblastoma

## TL;DR

This study identifies ASGR2 and CLEC12A as key C-type lectins linked to immunosuppression and poor prognosis in glioblastoma patients.

## Contribution

The novel contribution is identifying ASGR2 and CLEC12A as prognostic C-type lectin hubs in glioblastoma through network-based analysis and validation.

## Key findings

- ASGR2 and CLEC12A are central hubs in a C-type lectin network associated with immunosuppressive cells in glioblastoma.
- Expression of ASGR2 and CLEC12A correlates with poor patient prognosis and immunosuppressive myeloid subsets.
- Findings were validated using tumor and liquid biopsies from 20 glioblastoma patients.

## Abstract

In glioblastoma, the strong immunosuppression of the tumor immune microenvironment fosters tumor aggressiveness and decreases the effectiveness of therapeutic interventions, including immunotherapies. An intricate network of connections among tumor cells, stroma and infiltrating immune cells sustains immunosuppression. Lectins are immunoregulatory glycan-binding receptors contributing to immunosuppression. Their targeting is proposed as an appealing strategy for anti-cancer therapy. In this work, network-based approaches were exploited to identify a lectin profile that could dissect the complexity of tumor-immunity interactions in glioblastoma. Differential co-expression analysis, employing TCGA, CGGA and GTEx databases (145, 133 and 255 samples, respectively), identified a cluster of novel C-type lectins, with ASGR2 and CLEC12A as principal hubs. Furthermore, TIMER2.0 analysis revealed that their expression was significantly associated with immunosuppressive cells. ASGR2 and CLEC12A expression was also validated by cytofluorimetric analysis on both tumor and liquid biopsies from 20 glioblastoma patients. We report that ASGR2 and CLEC12A C-type lectins are associated with tumor-infiltrating immunosuppressive myeloid subsets and discriminate patients’ poor prognosis. These results suggest that C-type lectins may contribute to the immunosuppressive network sustained by infiltrating myeloid immune cells in GB, resulting in exploitable targets for therapeutic interventions.