Fibroblast-derived IL33 facilitates breast cancer metastasis by modifying the immune microenvironment and driving type 2 immunity

Ophir Shani, Tatiana Vorobyov, Lea Monteran, Dor Lavie, Noam Cohen, Yael Raz, Galia Tsarfaty, Camila Avivi, Iris Barshack, Neta Erez

Research output: Contribution to journalArticlepeer-review

Abstract

Lungs are one of the main sites of breast cancer metastasis. The metastatic microenvironment is essential to facilitate growth of disseminated tumor cells. Cancer-associated fibroblasts (CAF) are prominent players in the microenvironment of breast cancer. However, their role in the formation of a permissive metastatic niche is unresolved. Here we show that IL33 is upregulated in metastases-associated fibroblasts in mouse models of spontaneous breast cancer metastasis and in patients with breast cancer with lung metastasis. Upregulation of IL33 instigated type 2 inflammation in the metastatic microenvironment and mediated recruitment of eosinophils, neutrophils, and inflammatory monocytes to lung metastases. Importantly, targeting of IL33 in vivo resulted in inhibition of lung metastasis and significant attenuation of immune cell recruitment and type 2 immunity. These findings demonstrate a key function of IL33 in facilitating lung metastatic relapse by modulating the immune microenvironment. Our study shows a novel interaction axis between CAF and immune cells and reveals the central role of CAF in establishing a hospitable inflammatory niche in lung metastasis.

Original languageEnglish
Pages (from-to)5317-5329
Number of pages13
JournalCancer Research
Volume80
Issue number23
Early online date6 Oct 2020
DOIs
StatePublished - 1 Dec 2020

Fingerprint

Dive into the research topics of 'Fibroblast-derived IL33 facilitates breast cancer metastasis by modifying the immune microenvironment and driving type 2 immunity'. Together they form a unique fingerprint.

Cite this