| Literature DB >> 28082403 |
Sheeba Irshad1, Fabian Flores-Borja1,2, Katherine Lawler2,3, James Monypenny2, Rachel Evans2, Victoria Male1, Peter Gordon1,2, Anthony Cheung2, Patrycja Gazinska1, Farzana Noor1, Felix Wong2, Anita Grigoriadis1, Gilbert O Fruhwirth2,4, Paul R Barber5, Natalie Woodman6, Dominic Patel7, Manuel Rodriguez-Justo7, Julie Owen6, Stewart G Martin8, Sarah E Pinder6,9, Cheryl E Gillett6,9, Simon P Poland2, Simon Ameer-Beg2, Frank McCaughan10,11, Leo M Carlin4, Uzma Hasan7, David R Withers12, Peter Lane12, Borivoj Vojnovic5, Sergio A Quezada13, Paul Ellis14, Andrew N J Tutt1,15, Tony Ng16,2,13.
Abstract
Cancer cells tend to metastasize first to tumor-draining lymph nodes, but the mechanisms mediating cancer cell invasion into the lymphatic vasculature remain little understood. Here, we show that in the human breast tumor microenvironment (TME), the presence of increased numbers of RORγt+ group 3 innate lymphoid cells (ILC3) correlates with an increased likelihood of lymph node metastasis. In a preclinical mouse model of breast cancer, CCL21-mediated recruitment of ILC3 to tumors stimulated the production of the CXCL13 by TME stromal cells, which in turn promoted ILC3-stromal interactions and production of the cancer cell motile factor RANKL. Depleting ILC3 or neutralizing CCL21, CXCL13, or RANKL was sufficient to decrease lymph node metastasis. Our findings establish a role for RORγt+ILC3 in promoting lymphatic metastasis by modulating the local chemokine milieu of cancer cells in the TME. Cancer Res; 77(5); 1083-96. ©2017 AACR. ©2017 American Association for Cancer Research.Entities:
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Year: 2017 PMID： 28082403 DOI： 10.1158/0008-5472.CAN-16-0598
Source DB: PubMed Journal: Cancer Res ISSN： 0008-5472 Impact factor: 12.701