RORγt+ Innate Lymphoid Cells Promote Lymph Node Metastasis of Breast Cancers.
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ICR Authors
Authors
Irshad, S
Flores-Borja, F
Lawler, K
Monypenny, J
Evans, R
Male, V
Gordon, P
Cheung, A
Gazinska, P
Noor, F
Wong, F
Grigoriadis, A
Fruhwirth, GO
Barber, PR
Woodman, N
Patel, D
Rodriguez-Justo, M
Owen, J
Martin, SG
Pinder, SE
Gillett, CE
Poland, SP
Ameer-Beg, S
McCaughan, F
Carlin, LM
Hasan, U
Withers, DR
Lane, P
Vojnovic, B
Quezada, SA
Ellis, P
Tutt, ANJ
Ng, T
Flores-Borja, F
Lawler, K
Monypenny, J
Evans, R
Male, V
Gordon, P
Cheung, A
Gazinska, P
Noor, F
Wong, F
Grigoriadis, A
Fruhwirth, GO
Barber, PR
Woodman, N
Patel, D
Rodriguez-Justo, M
Owen, J
Martin, SG
Pinder, SE
Gillett, CE
Poland, SP
Ameer-Beg, S
McCaughan, F
Carlin, LM
Hasan, U
Withers, DR
Lane, P
Vojnovic, B
Quezada, SA
Ellis, P
Tutt, ANJ
Ng, T
Document Type
Journal Article
Date
2017-03-01
Date Accepted
2016-12-10
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.
Citation
Cancer Research, 2017, 77 (5), pp. 1083 - 1096
Source Title
Publisher
AMER ASSOC CANCER RESEARCH
ISSN
0008-5472
eISSN
1538-7445