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

Irshad, S; Flores-Borja, F; Lawler, K; Monypenny, J; Evans, R; Male, V; Gordon, P; ... Ng, T; + view all (2017) RORγt+ innate lymphoid cells promote lymph node metastasis of breast cancers. Cancer Research , 77 (5) pp. 1083-1096. 10.1158/0008-5472.CAN-16-0598. Green open access

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Abstract

Cancer cells tend to metastasize first to tumor-draining lymph nodes (LN), 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 LN 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 LN 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.

Type: Article
Title: RORγt+ innate lymphoid cells promote lymph node metastasis of breast cancers
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1158/0008-5472.CAN-16-0598
Publisher version: http://dx.doi.org/10.1158/0008-5472.CAN-16-0598
Language: English
Additional information: Copyright ©2017, American Association for Cancer Research.
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Pathology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
URI: http://discovery.ucl.ac.uk/id/eprint/1537221
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