ILC3 cells promote the proliferation and invasion of pancreatic cancer cells through IL-22/AKT signaling
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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.
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.
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.
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.
KeywordsILC3 Pancreatic cancer IL-22 IL-22R AKT signaling
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.
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.
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 was obtained from all patients.
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