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Sorafenib may enhance antitumour efficacy in hepatocellular carcinoma patients by modulating the proportions and functions of natural killer cells

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Summary

Dysfunction of natural killer (NK) cells is associated with poor prognosis in hepatocellular carcinoma (HCC). We explored the phenotypic and functional characteristics of peripheral blood NK cells in HCC patients following sorafenib treatment.Peripheral blood samples were collected from 60 HCC patients in a single centre (2015~2017) and 45 healthy donors. The percentage and cytoplasmic granule production of NK cells were analysed. Subset proportions were evaluated for their associations with the modified Response Evaluation Criteria in Solid Tumors (mRECIST), time to progression, and median overall survival (OS).Compared with baseline, the percentages of total and CD56dimCD16+ NK cells increased after two months of treatment, while the percentage of CD56brightCD16− NK cells decreased, leading to a dramatically reduced ratio of CD56bright and CD56dim NK cells (ratiobri/dim). Patients with low ratiobri/dim exhibited better mRECIST responses and longer median OS than those with high ratiobri/dim. The expression levels of granzyme B and perforin in total NK cells and in both subsets of cells were increased after treatment.This study showed that sorafenib could affect the proportions and functions of peripheral CD56brightCD16− and CD56dimCD16+ NK cells, which was associated with the outcomes including OS of HCC patients.

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Abbreviations

NK cell:

Natural killer cell

HCC:

HEPATOCELLULAR carcinoma

VEGFR:

Vascular endothelial growth factor receptor

PDGFR-β:

Platelet-derived growth factor receptor β

TAM:

Tumor-associated macrophages

IFN-γ:

Interferon-γ

HCV:

Hepatitis C virus

mRECIST:

Modified Response Evaluation Criteria in Solid Tumors

OS:

Overall survival

AASLD:

American Association for the study of Liver Disease

BCLC:

Barcelona Clinic Liver Cancer

ECOG:

Eastern Cooperative Oncology Group

HIV:

Human immunodeficiency virus

AEs:

Adverse events

CT:

Contrast-enhanced computer tomography

CR:

Complete response

PR:

Partial response

SD:

Stable disease

PD:

Progressive disease

TTP:

Time to progression

PBMCs:

Peripheral blood mononuclear cells

PMA:

Phorbol myristate acetate

ROC:

Receiver operating characteristic

ADCC:

Antibody-dependent cellular cytotoxicity

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Funding

This study was supported by grants from the National Natural Science Foundation of China (81420108020) for Prof. Guohong Han.

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Authors and Affiliations

  1. Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China

    Jie Hu, Enxin Wang, Lei Liu, Qiuhe Wang, Dongdong Xia, Wei Bai, Jun Tie, Xiaomei Li, Jie Yuan, Jing Niu, Kai Li, Chuangye He, Wengang Guo, Yong Lv, Hui Chen, Xulong Yuan, Tianlei Yu, Zhengyu Wang, Bohan Luo, Na Han, Ying Zhu, Zhanxin Yin & Guohong Han

  2. Department of Immunology, Fourth Military Medical University, Xi’an, China

    Shuya Yang, Dongbo Jiang, Jingqi Shi, Yuanjie Sun, Jing Wang, Chunmei Zhang & Kun Yang

  3. State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Disease and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China

    Daiming Fan

  4. Department of Radiology, Northwestern University, Chicago, IL, USA

    Zhuoli Zhang

Authors
  1. Jie Hu
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  2. Enxin Wang
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  3. Lei Liu
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  4. Qiuhe Wang
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  5. Dongdong Xia
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  6. Wei Bai
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  7. Jun Tie
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  8. Xiaomei Li
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  9. Jie Yuan
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  10. Shuya Yang
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  11. Dongbo Jiang
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  12. Jingqi Shi
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  13. Yuanjie Sun
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  14. Jing Wang
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  16. Jing Niu
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  17. Kai Li
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  18. Chuangye He
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  19. Wengang Guo
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  21. Hui Chen
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  22. Xulong Yuan
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  23. Tianlei Yu
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  29. Daiming Fan
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  30. Zhuoli Zhang
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  31. Kun Yang
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  32. Guohong Han
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Corresponding authors

Correspondence to Kun Yang or Guohong Han.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Hu, J., Wang, E., Liu, L. et al. Sorafenib may enhance antitumour efficacy in hepatocellular carcinoma patients by modulating the proportions and functions of natural killer cells. Invest New Drugs 38, 1247–1256 (2020). https://doi.org/10.1007/s10637-019-00885-2

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  • DOI: https://doi.org/10.1007/s10637-019-00885-2

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