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RORγt+ innate lymphoid cells promote lymph node metastasis of breast cancers

Irshad, Sheeba; Flores-Borja, Fabian; Lawler, Katherine; Monypenny, James; Evans, Rachel; Male, Victoria; Gordon, Peter; Cheung, Anthony; Gazinska, Patrycja; Noor, Farzana; Wong, Felix; Grigoriadis, Anita; Fruhwirth, Gilbert O.; Barber, Paul R.; Woodman, Natalie; Martin, Stewart G.

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Sheeba Irshad

Fabian Flores-Borja

Katherine Lawler

James Monypenny

Rachel Evans

Victoria Male

Peter Gordon

Anthony Cheung

Patrycja Gazinska

Farzana Noor

Felix Wong

Anita Grigoriadis

Gilbert O. Fruhwirth

Paul R. Barber

Natalie Woodman

Professor of Cancer and Radiation Biology


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.


Irshad, S., Flores-Borja, F., Lawler, K., Monypenny, J., Evans, R., Male, V., …Martin, S. G. (2017). RORγt+ innate lymphoid cells promote lymph node metastasis of breast cancers. Cancer Research, 77(5), 1083-1096.

Journal Article Type Article
Acceptance Date Dec 10, 2016
Online Publication Date Jan 12, 2017
Publication Date Mar 31, 2017
Deposit Date May 24, 2017
Publicly Available Date May 24, 2017
Journal Cancer Research
Print ISSN 0008-5472
Electronic ISSN 1538-7445
Publisher American Association for Cancer Research
Peer Reviewed Peer Reviewed
Volume 77
Issue 5
Pages 1083-1096
Public URL
Publisher URL
Additional Information 33 authors in total.


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