NCR group 3 innate lymphoid cells orchestrate IL-23/IL-17 axis to promote hepatocellular carcinoma development

Yonghao Liu, Yuan Song, Dandan Lin, Lei Lei, Yu Mei, Ziqi Jin, Huanle Gong, Ying Zhu, Bo Hu, Yinsheng Zhang, Lixiang Zhao, Huey Yee Teo, Ju Qiu, Wen Jiang, Chen Dong, Depei Wu, Yuhui Huang, Haiyan Liu

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: Innate lymphoid cells (ILCs) are a newly discovered family of immune cells that have similar cytokine-secreting profiles as T helper cell subsets. Although ILCs are critical for host defense against infections and tissue homeostasis, their roles in tumor development are not well established. Methods: We studied the function of ILC3 cells in the liver for the development of hepatocellular carcinoma (HCC) in murine HCC models using flow cytometry, adoptive transfer, and in vitro functional assays. Findings: We found that ILC3 lacking the natural cytotoxicity-triggering receptor (NCR ILC3) promoted the development of HCC in response to interleukin 23 (IL-23). IL-23 serum level is elevated in HCC patients and its high expression is associated with poor clinical outcomes. We found that IL-23 could promote tumor development in murine HCC tumor models. IL-23 promoted the expansion of NCR ILC3 and its differentiation from group 1 ILCs (ILC1s). Furthermore, NCR ILC3 initiated IL-17 production upon IL-23 stimulation and directly inhibited CD8 + T cell immunity by promoting lymphocyte apoptosis and limiting their proliferation. Interpretation: Together, our findings suggest that NCR ILC3 initiates the IL-17-rich immunosuppressive tumor microenvironment and promotes the development of HCC, thus may serve as a promising target for future cancer immunotherapy. Fund: This work was supported by grants from National Natural Science Foundation of China (81471586, 81571556), the Priority Academic Program Development of Jiangsu Higher Education Institutions, the collaborative Innovation Center of Hematology, start-up grant from National University of Singapore, the Cancer Prevention and Research Institute of Texas CPRIT (RR180017), and the National Cancer Institute's Cancer Center Support (Core) Grant CA016672 (to The University of Texas MD Anderson Cancer Center).

Original languageEnglish (US)
Pages (from-to)333-344
Number of pages12
JournalEBioMedicine
Volume41
DOIs
StatePublished - Mar 2019
Externally publishedYes

Fingerprint

Interleukin-23
Interleukin-17
Hepatocellular Carcinoma
Lymphocytes
Tumors
Natural Cytotoxicity Triggering Receptors
Neoplasms
Tissue homeostasis
Organized Financing
Natural sciences
T-cells
Flow cytometry
Immunosuppressive Agents
Liver
Natural Science Disciplines
Program Development
Tumor Microenvironment
Assays
National Cancer Institute (U.S.)
Adoptive Transfer

Keywords

  • HCC
  • IL-17
  • IL-23
  • ILC
  • Tumor microenvironment

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

NCR group 3 innate lymphoid cells orchestrate IL-23/IL-17 axis to promote hepatocellular carcinoma development . / Liu, Yonghao; Song, Yuan; Lin, Dandan; Lei, Lei; Mei, Yu; Jin, Ziqi; Gong, Huanle; Zhu, Ying; Hu, Bo; Zhang, Yinsheng; Zhao, Lixiang; Teo, Huey Yee; Qiu, Ju; Jiang, Wen; Dong, Chen; Wu, Depei; Huang, Yuhui; Liu, Haiyan.

In: EBioMedicine, Vol. 41, 03.2019, p. 333-344.

Research output: Contribution to journalArticle

Liu, Y, Song, Y, Lin, D, Lei, L, Mei, Y, Jin, Z, Gong, H, Zhu, Y, Hu, B, Zhang, Y, Zhao, L, Teo, HY, Qiu, J, Jiang, W, Dong, C, Wu, D, Huang, Y & Liu, H 2019, ' NCR group 3 innate lymphoid cells orchestrate IL-23/IL-17 axis to promote hepatocellular carcinoma development ', EBioMedicine, vol. 41, pp. 333-344. https://doi.org/10.1016/j.ebiom.2019.02.050
Liu, Yonghao ; Song, Yuan ; Lin, Dandan ; Lei, Lei ; Mei, Yu ; Jin, Ziqi ; Gong, Huanle ; Zhu, Ying ; Hu, Bo ; Zhang, Yinsheng ; Zhao, Lixiang ; Teo, Huey Yee ; Qiu, Ju ; Jiang, Wen ; Dong, Chen ; Wu, Depei ; Huang, Yuhui ; Liu, Haiyan. / NCR group 3 innate lymphoid cells orchestrate IL-23/IL-17 axis to promote hepatocellular carcinoma development In: EBioMedicine. 2019 ; Vol. 41. pp. 333-344.
@article{44a7a57e3028437eab0b080b59cd5ec2,
title = "NCR − group 3 innate lymphoid cells orchestrate IL-23/IL-17 axis to promote hepatocellular carcinoma development",
abstract = "Background: Innate lymphoid cells (ILCs) are a newly discovered family of immune cells that have similar cytokine-secreting profiles as T helper cell subsets. Although ILCs are critical for host defense against infections and tissue homeostasis, their roles in tumor development are not well established. Methods: We studied the function of ILC3 cells in the liver for the development of hepatocellular carcinoma (HCC) in murine HCC models using flow cytometry, adoptive transfer, and in vitro functional assays. Findings: We found that ILC3 lacking the natural cytotoxicity-triggering receptor (NCR − ILC3) promoted the development of HCC in response to interleukin 23 (IL-23). IL-23 serum level is elevated in HCC patients and its high expression is associated with poor clinical outcomes. We found that IL-23 could promote tumor development in murine HCC tumor models. IL-23 promoted the expansion of NCR − ILC3 and its differentiation from group 1 ILCs (ILC1s). Furthermore, NCR − ILC3 initiated IL-17 production upon IL-23 stimulation and directly inhibited CD8 + T cell immunity by promoting lymphocyte apoptosis and limiting their proliferation. Interpretation: Together, our findings suggest that NCR − ILC3 initiates the IL-17-rich immunosuppressive tumor microenvironment and promotes the development of HCC, thus may serve as a promising target for future cancer immunotherapy. Fund: This work was supported by grants from National Natural Science Foundation of China (81471586, 81571556), the Priority Academic Program Development of Jiangsu Higher Education Institutions, the collaborative Innovation Center of Hematology, start-up grant from National University of Singapore, the Cancer Prevention and Research Institute of Texas CPRIT (RR180017), and the National Cancer Institute's Cancer Center Support (Core) Grant CA016672 (to The University of Texas MD Anderson Cancer Center).",
keywords = "HCC, IL-17, IL-23, ILC, Tumor microenvironment",
author = "Yonghao Liu and Yuan Song and Dandan Lin and Lei Lei and Yu Mei and Ziqi Jin and Huanle Gong and Ying Zhu and Bo Hu and Yinsheng Zhang and Lixiang Zhao and Teo, {Huey Yee} and Ju Qiu and Wen Jiang and Chen Dong and Depei Wu and Yuhui Huang and Haiyan Liu",
year = "2019",
month = "3",
doi = "10.1016/j.ebiom.2019.02.050",
language = "English (US)",
volume = "41",
pages = "333--344",
journal = "EBioMedicine",
issn = "2352-3964",
publisher = "Elsevier BV",

}

TY - JOUR

T1 - NCR − group 3 innate lymphoid cells orchestrate IL-23/IL-17 axis to promote hepatocellular carcinoma development

AU - Liu, Yonghao

AU - Song, Yuan

AU - Lin, Dandan

AU - Lei, Lei

AU - Mei, Yu

AU - Jin, Ziqi

AU - Gong, Huanle

AU - Zhu, Ying

AU - Hu, Bo

AU - Zhang, Yinsheng

AU - Zhao, Lixiang

AU - Teo, Huey Yee

AU - Qiu, Ju

AU - Jiang, Wen

AU - Dong, Chen

AU - Wu, Depei

AU - Huang, Yuhui

AU - Liu, Haiyan

PY - 2019/3

Y1 - 2019/3

N2 - Background: Innate lymphoid cells (ILCs) are a newly discovered family of immune cells that have similar cytokine-secreting profiles as T helper cell subsets. Although ILCs are critical for host defense against infections and tissue homeostasis, their roles in tumor development are not well established. Methods: We studied the function of ILC3 cells in the liver for the development of hepatocellular carcinoma (HCC) in murine HCC models using flow cytometry, adoptive transfer, and in vitro functional assays. Findings: We found that ILC3 lacking the natural cytotoxicity-triggering receptor (NCR − ILC3) promoted the development of HCC in response to interleukin 23 (IL-23). IL-23 serum level is elevated in HCC patients and its high expression is associated with poor clinical outcomes. We found that IL-23 could promote tumor development in murine HCC tumor models. IL-23 promoted the expansion of NCR − ILC3 and its differentiation from group 1 ILCs (ILC1s). Furthermore, NCR − ILC3 initiated IL-17 production upon IL-23 stimulation and directly inhibited CD8 + T cell immunity by promoting lymphocyte apoptosis and limiting their proliferation. Interpretation: Together, our findings suggest that NCR − ILC3 initiates the IL-17-rich immunosuppressive tumor microenvironment and promotes the development of HCC, thus may serve as a promising target for future cancer immunotherapy. Fund: This work was supported by grants from National Natural Science Foundation of China (81471586, 81571556), the Priority Academic Program Development of Jiangsu Higher Education Institutions, the collaborative Innovation Center of Hematology, start-up grant from National University of Singapore, the Cancer Prevention and Research Institute of Texas CPRIT (RR180017), and the National Cancer Institute's Cancer Center Support (Core) Grant CA016672 (to The University of Texas MD Anderson Cancer Center).

AB - Background: Innate lymphoid cells (ILCs) are a newly discovered family of immune cells that have similar cytokine-secreting profiles as T helper cell subsets. Although ILCs are critical for host defense against infections and tissue homeostasis, their roles in tumor development are not well established. Methods: We studied the function of ILC3 cells in the liver for the development of hepatocellular carcinoma (HCC) in murine HCC models using flow cytometry, adoptive transfer, and in vitro functional assays. Findings: We found that ILC3 lacking the natural cytotoxicity-triggering receptor (NCR − ILC3) promoted the development of HCC in response to interleukin 23 (IL-23). IL-23 serum level is elevated in HCC patients and its high expression is associated with poor clinical outcomes. We found that IL-23 could promote tumor development in murine HCC tumor models. IL-23 promoted the expansion of NCR − ILC3 and its differentiation from group 1 ILCs (ILC1s). Furthermore, NCR − ILC3 initiated IL-17 production upon IL-23 stimulation and directly inhibited CD8 + T cell immunity by promoting lymphocyte apoptosis and limiting their proliferation. Interpretation: Together, our findings suggest that NCR − ILC3 initiates the IL-17-rich immunosuppressive tumor microenvironment and promotes the development of HCC, thus may serve as a promising target for future cancer immunotherapy. Fund: This work was supported by grants from National Natural Science Foundation of China (81471586, 81571556), the Priority Academic Program Development of Jiangsu Higher Education Institutions, the collaborative Innovation Center of Hematology, start-up grant from National University of Singapore, the Cancer Prevention and Research Institute of Texas CPRIT (RR180017), and the National Cancer Institute's Cancer Center Support (Core) Grant CA016672 (to The University of Texas MD Anderson Cancer Center).

KW - HCC

KW - IL-17

KW - IL-23

KW - ILC

KW - Tumor microenvironment

UR - http://www.scopus.com/inward/record.url?scp=85062145073&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85062145073&partnerID=8YFLogxK

U2 - 10.1016/j.ebiom.2019.02.050

DO - 10.1016/j.ebiom.2019.02.050

M3 - Article

C2 - 30827928

AN - SCOPUS:85062145073

VL - 41

SP - 333

EP - 344

JO - EBioMedicine

JF - EBioMedicine

SN - 2352-3964

ER -