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ILC3 cells promote the proliferation and invasion of pancreatic cancer cells through IL-22/AKT signaling

  • X. Xuan
  • J. Zhou
  • Z. Tian
  • Y. Lin
  • J. Song
  • Z. Ruan
  • B. NiEmail author
  • H. ZhaoEmail author
  • W. YangEmail author
Research Article
  • 98 Downloads
Part of the following topical collections:
  1. The Immune System and Cancer\Immunotherapy

Abstract

Purpose

Type 3 innate lymphocytes (ILC3s) are reported to be involved in lung cancer, possibly by producing interleukin-22 (IL-22). However, whether ILC3s and their secreted IL-22 molecules contribute to the pathogenesis of pancreatic cancer (PC) remains unclear. To this end, in this study, we investigated the effects and possible mechanisms of ILC3s on PC pathogenesis.

Method

The IL-22 and IL-2i2R levels and the ILC3s’ frequency in cancer tissues from PC patients and in peripheral blood from PC patients and healthy controls were analyzed by flow cytometry, immunochemistry, or immunofluorescence. The effects of IL-22-induced AKT signaling on the proliferation, invasion, and migration of PC cells were examined by co-culturing PC cell lines with ILC3s isolated from PC tissues, with or without the addition of neutralizing IL-22 antibody, IL-22R antibody or AKT inhibitor.

Results

Our results showed that IL-22 and ILC3s were significantly upregulated in the PBMCs and cancer tissues of PC patients, and the IL-22R level was increased in PC cells. The increased frequency of ILC3s was positively correlated with the clinical features of PC patients. Co-culture experiments indicated that ILC3s promoted the proliferation, invasion, and migration of PC cell lines by secreting IL-22 to activate AKT signaling because IL-22/IL-22R or AKT blockage markedly counteracted such effects on PC cells.

Conclusion

Our data demonstrated that ILC3s may promote PC pathogenesis through IL-22/IL-22R-AKT signaling, suggesting a potential intervention target for PC treatment in the future.

Keywords

ILC3 Pancreatic cancer IL-22 IL-22R AKT signaling 

Notes

Author contributions

BN, WY. and HZ conceived and directed the project. XX performed most experiments. JS, ZT, ZR, and YL contributed to the experiments or data analysis. BN wrote the manuscript.

Funding

This work was supported by grants from the National Key Research and Development Plan of China (No. 2016YFA0502203), the National Science Foundation of China (No. 81670534 and 81471531), Guangxi Natural Science Foundation Project (No. 2015GXNSFAA139170) and Medical Scientific and Technological Innovation Funds of Southwest Hospital (No. SWH2016LHYS-04).

Compliance with ethical standards

Conflict of interest

All authors declare no financial conflict of interest.

Ethical approval

The study was approved by the ethics committee of the Southwest Hospital, Chongqing, China.

Human and animal rights

All procedures performed in studies involving human participants were in accordance with the ethics committee of the Southwest Hospital and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all patients.

Supplementary material

12094_2019_2160_MOESM1_ESM.docx (205 kb)
Supplementary file1 (DOCX 204 kb)
12094_2019_2160_MOESM2_ESM.docx (339 kb)
Supplementary file2 (DOCX 338 kb)
12094_2019_2160_MOESM3_ESM.docx (98 kb)
Supplementary file3 (DOCX 97 kb)

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Copyright information

© Federación de Sociedades Españolas de Oncología (FESEO) 2019

Authors and Affiliations

  1. 1.Department of Pathophysiology, College of High Altitude Military MedicineThird Military Medical UniversityChongqingChina
  2. 2.Department of Kidney, Southwest HospitalArmy Medical University (Third Military Medical University)ChongqingChina
  3. 3.Institute of Immunology, PLAThird Military Medical UniversityChongqingChina
  4. 4.Bellevue Christian High SchoolBellevueUSA
  5. 5.Department of Microbial Pathogenesis and ImmunologyTexas A&M University Health Science CenterCollege StationUSA
  6. 6.Department of Oncology and Southwest Cancer Center, Southwest HospitalThird Military Medical University (Army Medical University)ChongqingChina
  7. 7.Department of DermatologyThe 181th Hospital of PLAGuilinChina

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