ROR gamma t(+) innate lymphoid cells promote lymph node metastasis of breast cancers
File(s)
Accepted version
Author(s)
Type
Journal Article
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.
Date Issued
2017-03-01
Date Acceptance
2016-12-10
Citation
Cancer Research, 2017, 77 (5), pp.1083-1096
ISSN
0008-5472
Publisher
American Association for Cancer Research
Start Page
1083
End Page
1096
Journal / Book Title
Cancer Research
Volume
77
Issue
5
Copyright Statement
© 2017 American Association for Cancer Research.
Sponsor
Medical Research Council (MRC)
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000396011100005&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
MR/M01245X/1
Subjects
Science & Technology
Life Sciences & Biomedicine
Oncology
TISSUE-INDUCER CELLS
MESENCHYMAL TRANSITION
CHEMOKINE CXCL13
SECONDARY
TUMORS
EXPRESSION
STROMA
BASAL
ORGANOGENESIS
INFILTRATION
Publication Status
Published
Date Publish Online
2017-01-12