Aberrant expression of p-STAT3 in peripheral blood CD4+ and CD8+ T cells related to hepatocellular carcinoma development

Wang, Xu; Xin, Wenbin; Zhang, Hua; Zhang, Fengmei; Gao, Meilan; Yuan, Lingling; Xu, Xiaoyan; Hu, Xuemei; Zhao, Mengnan

doi:10.3892/mmr.2014.2510

Cited by 17 publications

(11 citation statements)

References 38 publications

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“…Tumor-resident CD8 + T-cells express high levels of IL-10R, leading to high levels of activated pSTAT3 and pSTAT1 in response to IL-10 [97]. In contrast, circulating CD8 + T-cells from peripheral blood of HCC patients present high amounts of pSTAT3 which is correlated with high amount of IL-4, IL-6 and IL-10 and low quantity of IFN-γ which may result in abnormal immune surveillance against tumor cells [98]. In murine CD8 + T-cells, STAT3 has been shown to inhibit both IFN-γ-mediated CXCL10 production by myeloid cells and CD8 + T-cells CXCR3 expression (the receptor of CXCL10), blocking the migration of these cells to the tumor site [60].…”

Section: Stat3 and T-cellsmentioning

confidence: 99%

STAT3, a Master Regulator of Anti-Tumor Immune Response

Rébé

Ghiringhelli

2019

Cancers

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Immune cells in the tumor microenvironment regulate cancer growth. Thus cancer progression is dependent on the activation or repression of transcription programs involved in the proliferation/activation of lymphoid and myeloid cells. One of the main transcription factors involved in many of these pathways is the signal transducer and activator of transcription 3 (STAT3). In this review we will focus on the role of STAT3 and its regulation, e.g., by phosphorylation or acetylation in immune cells and how it might impact immune cell function and tumor progression. Moreover, we will review the ability of STAT3 to regulate checkpoint inhibitors.

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Section: Stat3 and T-cellsmentioning

confidence: 99%

STAT3, a Master Regulator of Anti-Tumor Immune Response

Rébé

Ghiringhelli

2019

Cancers

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“…IL-4 and IL-10 are negative regulators in the antitumor immune responses, and they can inhibit IL-2, IL-12, IFN-γ, and TNF-α production by Th1 cells [30]. In the serum of patients with hepatocellular carcinoma and supernatants of peripheral monocytes cocultured with Huh7 cells, the levels of cytokines (IL-4, IL-6, and IL-10) could be upregulated, while the level of IFN-γ could be downregulated [17]. In the present study, co-culture with HBV-T cells also significantly reduced IFN-γ and TNF-α production but increased the secretion of IL-6 and IL-10 in HepG2.2.15 cells, while co-culture-induced alterations in cytokines production in HepG2.…”

Section: Discussionmentioning

confidence: 99%

Amygdalin promotes the activity of T cells to suppress the progression of HBV-related hepatocellular carcinoma via the JAK2/STAT3 signaling pathway

Wang

Zhang²,

Sun

et al. 2020

Preprint

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Background: Hepatitis B virus (HBV) infection is a high-risk factor of hepatocellular carcinoma (HCC) . Cellular immune responses are essential for HCC development, and the CD4+ and CD8+ T subtypes are identified as the primary anti-tumor immune cells. In the study, we investigated the effect and mechanism of amygdalin in the cellular immune response in HBV-related HCC and HCC progression. Methods: The cell proliferation was examined by MTT analysis. Cells metastasis ability was detected by Invasion and migration assays. Quantification of apoptotic cells was performed with Flow cytometer assay. The protein levels of p-STAT3, STAT3, p-JAK2, JAK2, caspase-3, cleaved caspase-3 were detected by performing immunoblotting assays. Results: We demonstrate that amygdalin treatment could rescue the HBV-T cell viability and IFN-γ and TNF-αproduction . In HBV-T cells, the MFI levels of CD8 + are lower than that in NC-T cells. Moreover, the phosphorylation levels of STAT3 and JAK2 are higher in HBV-T cells, compared to those in NC-T cells, and then reduced by amygdalin treatment. Co-culture with HBV-T cells could reduce IFN-γ and TNF-α, production while increase IL-6 and IL-10 production in HepG2.2.15 cells; these alterations could be partially reversed by amygdalin pretreatment. Finally, co-culture with HBV-T cells significantly promoted the cell viability, inhibited the apoptosis, and promoted the migration of HepG2.2.15 cells , and these alterations could be partially reversed by amygdalin treatment. Conclusion: Our findings provide a rationale for further studies on the functions and mechanism of amygdalin inhibiting HBV-related HCC cell proliferation, invasion, and migration via T cell-mediated tumor immunity.

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Section: Discussionmentioning

confidence: 99%

“…As we have mentioned, being increased in the CD4 + and CD8 + subtypes in peripheral blood of patients with hepatocellular carcinoma, the p-STAT3 expression can lead to aberrant immunological surveillance, thus promoting the development of hepatocellular carcinoma [17]. Here, the p-STAT3…”

Section: Effect Of Amygdalin On the Activation Of T Cells And The Phomentioning

confidence: 93%

Amygdalin promotes the activity of T cells to suppress the progression of HBV-related hepatocellular carcinoma via the JAK2/STAT3 signaling pathway

Wang

Zhang²,

Sun

et al. 2019

Preprint

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Purpose Hepatitis B virus (HBV) infection is a high-risk factor of hepatocellular carcinoma (HCC). Cellular immune responses are essential for HCC development, and the CD4+ and CD8+ T subtypes are identified as the primary anti-tumor immune cells. In the study, we investigated the effect and mechanism of amygdalin in the cellular immune response in HBV-related HCC and HCC progression.Methods The cell proliferation was examined by MTT analysis. Cells metastasis ability was detected by Invasion and migration assays. Quantification of apoptotic cells was performed with Flow cytometer assay. The protein levels of p-STAT3, STAT3, p-JAK2, and JAK2 were detected by performing immunoblotting assays.Results We demonstrate that amygdalin treatment could rescue the HBV-T cell viability and IFN-γ and TNF-αproduction. In HBV-T cells, the MFI levels of CD8+ are lower than that in NC-T cells. Moreover, the phosphorylation levels of STAT3 and JAK2 are higher in HBV-T cells, compared to those in NC-T cells, and then reduced by amygdalin treatment. Co-culture with HBV-T cells could reduce IFN-γ and TNF-α, production while increase IL-6 and IL-10 production in HepG2.2.15 cells; these alterations could be partially reversed by amygdalin pretreatment. Finally, co-culture with HBV-T cells significantly promoted the cell viability, inhibited the apoptosis, and promoted the migration of HepG2.2.15 cells, and these alterations could be partially reversed by amygdalin treatment.Conclusion Our findings provide a rationale for further studies on the functions and mechanism of amygdalin inhibiting HBV-related HCC cell proliferation, invasion, and migration via T cell-mediated tumor immunity.

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Aberrant expression of p-STAT3 in peripheral blood CD4+ and CD8+ T cells related to hepatocellular carcinoma development

Cited by 17 publications

References 38 publications

STAT3, a Master Regulator of Anti-Tumor Immune Response

STAT3, a Master Regulator of Anti-Tumor Immune Response

Amygdalin promotes the activity of T cells to suppress the progression of HBV-related hepatocellular carcinoma via the JAK2/STAT3 signaling pathway

Amygdalin promotes the activity of T cells to suppress the progression of HBV-related hepatocellular carcinoma via the JAK2/STAT3 signaling pathway

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