Dataset Information

GLIS1 intervention enhances anti-PD1 therapy for hepatocellular carcinoma by targeting SGK1-STAT3-PD1 pathway.

ABSTRACT:

Background

GLI-similar 1 (GLIS1) is one of of Krüppel-like zinc finger proteins, which are either stimulators or inhibitors of genetic transcription. Nevertheless, its effects on T cell were elusive.

Methods

In this study, we intend to explore the effects of GLIS1 on modulating the anticancer potency of CD8⁺ T cells in hepatocellular carcinoma (HCC). The expression of GLIS1 in CD8 peripheral blood mononuclear cell and CD8 tumor-infiltrating lymphocytes of HCC tissues was validated by quantificational real-time-PCR and flow cytometry. The anticancer potency of CD8⁺ T cells with GLIS1 knock down was confirmed in C57BL/6 mouse model and HCC patient-derived xenograft mice model. GLIS1^-/- C57BL/6 mice was applied to explore the effects GLIS1 on tumor immune microenvironment. Chromatin immunoprecipitation and RNA transcriptome sequencing analysis were both performed in GLIS1-knock down of CD8⁺ T cells.

Results

GLIS1 was upregulated in exhausted CD8⁺ T cells in HCC. GLIS1 downregulation in CD8⁺ T cells repressed cancer development, elevated the infiltrate ability of CD8⁺ T cells, mitigated CD8⁺ T cell exhaustion and ameliorated the anti-PD1 reaction of CD8⁺ T cells in HCC. The causal link beneath this included transcriptional regulation of SGK1-STAT3-PD1 pathway by GLIS1, thereby maintaining the abundant PD1 expression on the surface of CD8⁺ T cells.

Conclusion

Our study revealed that GLIS1 promoted CD8⁺ T cell exhaustion in HCC through transcriptional regulating SGK1-STAT3-PD1 pathway. Downregulating the expression of GLIS1 in CD8⁺ T cells exerted an effect with anti-PD1 treatment synergistically, revealing a prospective method for HCC immune therapy.

SUBMITTER: Rong D

PROVIDER: S-EPMC9930610 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Publications

GLIS1 intervention enhances anti-PD1 therapy for hepatocellular carcinoma by targeting SGK1-STAT3-PD1 pathway.

Rong Dawei D Wang Yuliang Y Liu Li L Cao Hengsong H Huang Tian T Liu Hanyuan H Hao Xiaopei X Sun Guangshun G Sun Guoqiang G Zheng Zhiying Z Kang Junwei J Xia Yongxiang Y Chen Ziyi Z Tang Weiwei W Wang Xuehao X

Journal for immunotherapy of cancer 20230201 2

<h4>Background</h4>GLI-similar 1 (GLIS1) is one of of Krüppel-like zinc finger proteins, which are either stimulators or inhibitors of genetic transcription. Nevertheless, its effects on T cell were elusive.<h4>Methods</h4>In this study, we intend to explore the effects of GLIS1 on modulating the anticancer potency of CD8<sup>+</sup> T cells in hepatocellular carcinoma (HCC). The expression of GLIS1 in CD8 peripheral blood mononuclear cell and CD8 tumor-infiltrating lymphocytes of HCC tissues wa ...[more]

PMID: 36787938

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Dataset Information

GLIS1 intervention enhances anti-PD1 therapy for hepatocellular carcinoma by targeting SGK1-STAT3-PD1 pathway.

Background

Methods

Results

Conclusion

Publications

GLIS1 intervention enhances anti-PD1 therapy for hepatocellular carcinoma by targeting SGK1-STAT3-PD1 pathway.

Similar Datasets

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