期刊
CANCER MEDICINE
卷 12, 期 4, 页码 4938-4950出版社
WILEY
DOI: 10.1002/cam4.5186
关键词
CHST11; hepatocellular carcinoma; prognosis; Treg cells
类别
This study found that CHST11 expression is upregulated in HCC and is associated with tumor progression and prognosis. It affects immune function in HCC by modulating pathways related to tumor growth, metastasis, and immune regulation, promoting Tregs infiltration and increasing PD-L1/PD-1 expression, resulting in immunosuppression. Targeting CHST11 may enhance the antineoplastic effect of immune checkpoint inhibitors.
Despite great advance has been made in multi-modality treatments for HCC patients, the effectiveness is far from satisfactory with worse survival outcome, which may be partly explainable by the anti-tumor deficiency of the immune system. It is necessary to clarify the molecular mechanism of HCC immunodeficiency. Here, we demonstrated that carbohydrate sulfotransferase 11 (CHST11) was upregulated in HCC and related to advanced TNM stage. HCC patients with TP53 mutation showed higher CHST11 expression. Survival analysis revealed that CHST11 was an independent prognostic biomarker in HCC. Cellular functional experiments indicated that knockdown of CHST11 in HCC inhibited cell proliferation and metastasis. Gene functional enrichment analyses indicated that CHST11 modulated pathways related to tumor growth, metastasis and immune regulation. Continuative immune-related analyses revealed that CHST11 expression facilitated Tregs infiltration in HCC and promoted the expression of checkpoints PD-L1/PD-1, resulting in the immunosuppression of HCC. Targeting CHST11 may inhibit Tregs infiltration and enhance the antineoplastic effect of immune checkpoint inhibitors, which provides a novel insight into the combination immunotherapy with Treg-modulating agents and PD-L1/PD-1 inhibitors.
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