ROR gamma t(+) innate lymphoid cells promote lymph node metastasis of breast cancers

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Title: ROR gamma t(+) innate lymphoid cells promote lymph node metastasis of breast cancers
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
Item 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.
Issue Date: 1-Mar-2017
Date of Acceptance: 10-Dec-2016
URI: http://hdl.handle.net/10044/1/70607
DOI: https://doi.org/10.1158/0008-5472.CAN-16-0598
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/Funder: Medical Research Council (MRC)
Funder's Grant Number: MR/M01245X/1
Keywords: Science & Technology
Life Sciences & Biomedicine
Oncology
TISSUE-INDUCER CELLS
MESENCHYMAL TRANSITION
CHEMOKINE CXCL13
SECONDARY
TUMORS
EXPRESSION
STROMA
BASAL
ORGANOGENESIS
INFILTRATION
Animals
Breast Neoplasms
Cell Line, Tumor
Chemokine CCL21
Chemokine CXCL13
Female
Humans
Immunity, Innate
Lymphatic Metastasis
Lymphocytes
Mammary Neoplasms, Experimental
Mice
Mice, Inbred BALB C
Mice, Transgenic
Neoplasm Metastasis
Orphan Nuclear Receptors
Triple Negative Breast Neoplasms
Lymphocytes
Cell Line, Tumor
Animals
Mice, Inbred BALB C
Mice, Transgenic
Humans
Mice
Breast Neoplasms
Mammary Neoplasms, Experimental
Neoplasm Metastasis
Lymphatic Metastasis
Female
Chemokine CXCL13
Chemokine CCL21
Immunity, Innate
Orphan Nuclear Receptors
Triple Negative Breast Neoplasms
Science & Technology
Life Sciences & Biomedicine
Oncology
TISSUE-INDUCER CELLS
MESENCHYMAL TRANSITION
CHEMOKINE CXCL13
SECONDARY
TUMORS
EXPRESSION
STROMA
BASAL
ORGANOGENESIS
INFILTRATION
Oncology & Carcinogenesis
1112 Oncology and Carcinogenesis
Publication Status: Published
Online Publication Date: 2017-01-12
Appears in Collections:Division of Surgery
National Heart and Lung Institute



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