Colorectal cancer cell-derived CCL20 recruits regulatory T cells to promote chemoresistance via FOXO1/CEBPB/NF-κB signaling

Journal for Immunotherapy of Cancer
Dan WangYi Zhang

Abstract

Colorectal cancer (CRC) is one of the most common forms of cancer worldwide. The tumor microenvironment plays a key role in promoting the occurrence of chemoresistance in solid cancers. Effective targets to overcome resistance are necessary to improve the survival and prognosis of CRC patients. This study aimed to evaluate the molecular mechanisms of the tumor microenvironment that might be involved in chemoresistance in patients with CRC. We evaluated the effects of CCL20 on chemoresistance of CRC by recruitment of regulatory T cells (Tregs) in vitro and in vivo. We found that the level of CCL20 derived from tumor cells was significantly higher in Folfox-resistant patients than in Folfox-sensitive patients. The high level of CCL20 was closely associated with chemoresistance and poor survival in CRC patients. Among the drugs in Folfox chemotherapy, we confirmed that 5-FU increased the expression of CCL20 in CRC. Moreover, CCL20 derived from 5-FU-resistant CRC cells promoted recruitment of Tregs. Tregs further enhanced the chemoresistance of CRC cells to 5-FU. FOXO1/CEBPB/NF-κB signaling was activated in CRC cells after 5-FU treatment and was required for CCL20 upregulation mediated by 5-FU. Furthermore, CCL20 blockade suppresse...Continue Reading

References

Apr 29, 1998·Nature·M Baggiolini
Nov 18, 2006·The Journal of Clinical Investigation·Roberto PivaGiorgio Inghirami
Mar 12, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Yeon Hee ParkDong Hwan Kim
Jan 13, 2010·Cold Spring Harbor Perspectives in Biology·Michael Karin
Mar 12, 2010·Nature·Massimo AmmiranteMichael Karin
Nov 17, 2010·Cancer Letters·Alexander ArltHeiner Schäfer
Jun 21, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Hasan KorkayaMax S Wicha
Jan 13, 2012·CA: a Cancer Journal for Clinicians·Rebecca SiegelAhmedin Jemal
Aug 2, 2012·Nature Reviews. Clinical Oncology·M Teresa Villanueva
Mar 20, 2013·Proceedings of the National Academy of Sciences of the United States of America·Margaret GilDanuta Kozbor
Oct 18, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Hemant K BidPeter J Houghton
Apr 16, 2014·Proceedings of the National Academy of Sciences of the United States of America·Julie L HeineckeDavid A Wink
Dec 22, 2015·Cellular and Molecular Life Sciences : CMLS·Alexandra Coomans de Brachène, Jean-Baptiste Demoulin
Jul 28, 2016·International Journal of Cancer. Journal International Du Cancer·Lifeng LiYi Zhang
Aug 21, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Anda-Alexandra CalinescuMaria Graciela Castro
Aug 30, 2016·World Journal of Gastroenterology : WJG·Tao HuChi Hin Cho
Sep 27, 2016·The Breast : Official Journal of the European Society of Mastology·Kobra VelaeiJafar Soleimani Rad
Dec 3, 2016·Science Translational Medicine·Natalia Arenas-RamirezOnur Boyman
Dec 6, 2016·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Eryong LuYuehui Wang
Feb 6, 2017·Oncotarget·Jamie D GardinerJoshua D Schiffman
May 30, 2017·Cytokine & Growth Factor Reviews·Luigi FattoreGennaro Ciliberto
Jul 12, 2017·The Journal of Clinical Investigation·Keehoon JungDai Fukumura
Jan 25, 2018·Cancer Immunology Research·Rafael SamaniegoPaloma Sánchez-Mateos
Feb 8, 2018·Translational Oncology·Jones GyamfiJunjeong Choi
Aug 3, 2018·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Long-Zi LiuQiang Gao
Oct 21, 2018·The Journal of Nutritional Biochemistry·Ganesan MuthusamyNagarajan Rajendra Prasad
Dec 12, 2018·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Chenglong ZhaoJianru Xiao

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Citations

Feb 26, 2020·Cells·Ahmad Adebayo IrekeolaRafidah Hanim Shueb
Jul 28, 2020·International Journal of Molecular Sciences·Suguru KadomotoAtsushi Mizokami
Jun 1, 2020·Cellular Oncology (Dordrecht)·Pan XieZhao-Qian Liu
May 28, 2020·Trends in Cancer·Emma C MaddenAfshin Samali
Jan 24, 2021·Cell Death Discovery·Dachuan ShenRuoyu Wang
Feb 13, 2021·Cancer Immunology, Immunotherapy : CII·Shasha LiuYi Zhang
Oct 30, 2020·International Journal of Molecular Sciences·Polina V ShnaiderVictoria O Shender
Jan 20, 2021·Clinical and Translational Medicine·Neng WangZhiyu Wang
Apr 12, 2021·Immunity·Aleksandra J OzgaAndrew D Luster
May 1, 2021·Cancers·Justine CinierChristine Ménétrier-Caux
May 1, 2021·Cancers·Elodie PramilAlexandre E Escargueil
May 6, 2021·Neuro-oncology Advances·Phillip KubicaMahua Dey
Jun 8, 2021·Frontiers in Cell and Developmental Biology·Yanghong NiXuelei Ma
Jun 21, 2021·Cancer Cell International·Guiyang CaiWei Sun
Jul 16, 2021·International Journal of Radiation Biology·Ayman Oweida, Benoit Paquette
Sep 21, 2021·Frontiers in Immunology·Saadia Ait SsiAbdallah Badou

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Methods Mentioned

BETA
flow cytometry
transfection
ELISA
xenografts
surgical resection

Software Mentioned

Graph Pad
cBioPortal for Genomics
Gene Set Enrichment Analysis ( GSEA )
Graph Pad Prism

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