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Tumor-intrinsic ST3GAL3 Activity Blunts Anti-tumor Immune and Drives Immunotherapy Resistance

ABSTRACT: ST3GAL3 is a α2,3-sialyltransferase and involves in α2,3 sialylation in tumors; however, its role in the tumorigenic capacity of malignant cells and anti-tumor immune remains largely unexplored. Here, HM1 cells were stably transfected using lentivirus expressing a shRNA targeting ST3GAL3 (HM1-shST3GAL3) or scramble shRNA as control (HM1-shControl). Then, HM1-shControl or HM1-shST3GAL3 cells were injected into the right flank of B6C3F1 mice using a 27 g needle. ST3GAL3 knockdown significantly compromised tumor growth at a immune-dependant manner. Mechanistically, ST3GAL3 knockdown enhances pro-inflammatory phenotype of macrophages, leading ultimately to activation and recruitmentof CD8+ T cells. Moreover, we identified ST3GAL3 as a potential novel biomarker for bevacizumab or immune checkpoint blockade (ICB) intervention. ST3GAL3 knockdown in tumors also be useful to improve cancer immunotherapies.

ORGANISM(S): Mus musculus

PROVIDER: GSE213219 | GEO | 2023/05/09

REPOSITORIES: GEO

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