Immune effector monocyte–neutrophil cooperation induced by the primary tumor prevents metastatic progression of breast cancer

Catharina Hagerling, Hugo Gonzalez, Kiarash Salari, Chih Yang Wang, Charlene Lin, Isabella Robles, Merel van Gogh, Annika Dejmek, Karin Jirström, Zena Werb

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24 引文 斯高帕斯(Scopus)

摘要

Metastatic behavior varies significantly among breast cancers. Mechanisms explaining why the majority of breast cancer patients never develop metastatic outgrowth are largely lacking but could underlie the development of novel immunotherapeutic target molecules. Here we show interplay between nonmetastatic primary breast cancer and innate immune response, acting together to control metastatic progression. The primary tumor systemically recruits IFNγ-producing immune effector monocytes to the lung. IFNγ up-regulates Tmem173/ STING in neutrophils and enhances their killing capacity. The immune effector monocytes and tumoricidal neutrophils target disseminated tumor cells in the lungs, preventing metastatic outgrowth. Importantly, our findings could underlie the development of immunotherapeutic target molecules that augment the function of immune effector monocytes and neutrophils.

原文英語
頁(從 - 到)21704-21714
頁數11
期刊Proceedings of the National Academy of Sciences of the United States of America
116
發行號43
DOIs
出版狀態已發佈 - 十月 22 2019

ASJC Scopus subject areas

  • 多學科

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