X Xuan1,2, J Zhou3, Z Tian3, Y Lin4, J Song5, Z Ruan6, B Ni7, H Zhao8, W Yang9. 1. Department of Pathophysiology, College of High Altitude Military Medicine, Third Military Medical University, Chongqing, 400038, China. 2. Department of Kidney, Southwest Hospital, Army Medical University (Third Military Medical University), 30 Gaotanyan Street, District Shapingba, Chongqing, 400038, China. 3. Institute of Immunology, PLA, Third Military Medical University, Chongqing, 400038, China. 4. Bellevue Christian High School, 1601 98th Ave NE, Bellevue, WA, 98004, USA. 5. Department of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center, College Station, TX, 77843, USA. 6. Department of Oncology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China. 7. Department of Pathophysiology, College of High Altitude Military Medicine, Third Military Medical University, Chongqing, 400038, China. 15991833423@163.com. 8. Department of Kidney, Southwest Hospital, Army Medical University (Third Military Medical University), 30 Gaotanyan Street, District Shapingba, Chongqing, 400038, China. zhaohw212@126.com. 9. Department of Dermatology, The 181th Hospital of PLA, No. 1 Xinqiaoyuan Road, Guilin, 541002, Guangxi Zhuang Autonomous Region, China. 1512638974@qq.com.
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.
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.
Entities:
Keywords:
AKT signaling; IL-22; IL-22R; ILC3; Pancreatic cancer
Authors: Daniel R Neill; See Heng Wong; Agustin Bellosi; Robin J Flynn; Maria Daly; Theresa K A Langford; Christine Bucks; Colleen M Kane; Padraic G Fallon; Richard Pannell; Helen E Jolin; Andrew N J McKenzie Journal: Nature Date: 2010-03-03 Impact factor: 49.962
Authors: Laurel A Monticelli; Gregory F Sonnenberg; Michael C Abt; Theresa Alenghat; Carly G K Ziegler; Travis A Doering; Jill M Angelosanto; Brian J Laidlaw; Cliff Y Yang; Taheri Sathaliyawala; Masaru Kubota; Damian Turner; Joshua M Diamond; Ananda W Goldrath; Donna L Farber; Ronald G Collman; E John Wherry; David Artis Journal: Nat Immunol Date: 2011-11 Impact factor: 25.606
Authors: Jeremy Goc; Mengze Lv; Nicholas J Bessman; Anne-Laure Flamar; Sheena Sahota; Hiroaki Suzuki; Fei Teng; Gregory G Putzel; Gerard Eberl; David R Withers; Janelle C Arthur; Manish A Shah; Gregory F Sonnenberg Journal: Cell Date: 2021-08-17 Impact factor: 66.850