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An imbalance between stellate cells and γδT cells contributes to hepatocellular carcinoma aggressiveness and recurrence

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Abstract

Purpose

The diagnostic potential of hepatic stellate cells (HSCs) and γδT cells for patients with hepatocellular carcinoma (HCC) and their synergistic contributions to the prognosis of these patients have not yet been investigated. The aim of this study was to elucidate the prognostic value of these cells in HCC.

Methods

The prognostic significance of the ratio of HSCs to γδT cells (SGR) was assessed in a total of 339 HCC patients undergoing resection. The correlation between the circulating tumor cell (CTC) level and SGR in 71 HCC patients was determined using the CellSearch system. In vitro experiments were performed to validate the synergistic effects of HSCs and γδT cells on hepatoma cells.

Results

Peritumoral SGR was closely associated with overall survival (OS) and recurrence-free survival (RFS) of HCC patients after resection. In the testing cohort, two nomograms incorporating the SGR were constructed for the prediction of OS and RFS. The predictive accuracy of the two nomograms was verified by the validation cohort. CTC levels were positively correlated with SGR (r = 0.479, p < 0.001). Among the patients with CTCs > 2/7.5 ml, those with a high SGR exhibited higher early recurrence rates than those with a low SGR. In vitro experiments revealed that the secretion of INF-γ, IL-17, and TNF-α from γδT cells was increased after culture with HSC-conditioned medium. In addition, γδT cells cultured with HSC-conditioned medium decreased the proliferative and invasive abilities of hepatoma cells.

Conclusions

The peritumoral SGR is related to aggressive tumor behavior and has a powerful predictive value in HCC. Early recurrence in patients with a high peritumoral SGR might be associated with high CTC levels.

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Acknowledgements

This research was supported by Science and Technology Research Program of Chongqing Municipal Education Commission (no. KJQN201800416), and Basic and Advanced Research Project of Science and Technology Commission of Chongqing Municipality (nos. cstc2017jcyjBX0010 and cstc2018jcyjAX0162).

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Author notes

  1. Bao-Yong Zhou, Jun-Hua Gong, Xiao-Yan Cai, Jia-Xing Wang, and Fang Luo have contributed equally to this work.

Authors and Affiliations

  1. Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, No. 1 Yixueyuan Rd, Chongqing, 400016, China

    Bao-Yong Zhou, Fang Luo, Cheng-You Du & Rui Liao

  2. Chongqing Key Laboratory of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China

    Jun-Hua Gong & Jian-Ping Gong

  3. Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China

    Jun-Hua Gong & Jian-Ping Gong

  4. Department of General Surgery, Gongli Hospital of Shanghai Pudong New Area, Shanghai, 200135, China

    Xiao-Yan Cai

  5. Department of Anesthesiology, Zhongshan Hospital of Fudan University, Shanghai, 200032, China

    Jia-Xing Wang

  6. Department of Pathology, Chongqing Medical University, Chongqing, 400016, China

    Ning Jiang

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  1. Bao-Yong Zhou
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  2. Jun-Hua Gong
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  7. Jian-Ping Gong
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Corresponding author

Correspondence to Rui Liao.

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Conflict of interest

Bao-Yong Zhou, Jun-Hua Gong, Xiao-Yan Cai, Jia-Xing Wang, Fang Luo, Ning Jiang, Jian-Ping Gong, Cheng-You Du, and Rui Liao declare that they have no competing interests.

Ethical approval

This study protocol conformed to the Ethics Committee at the First Affiliated Hospital of Chongqing Medical University and the ethical guidelines of the 1975 Helsinki Declaration and was approved, and written informed consents were obtained from all patients.

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Zhou, BY., Gong, JH., Cai, XY. et al. An imbalance between stellate cells and γδT cells contributes to hepatocellular carcinoma aggressiveness and recurrence. Hepatol Int 13, 631–640 (2019). https://doi.org/10.1007/s12072-019-09969-w

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  • DOI: https://doi.org/10.1007/s12072-019-09969-w

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