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

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)21704-21714
Number of pages11
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number43
DOIs
Publication statusPublished - Oct 22 2019

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Monocytes
Neutrophils
Breast Neoplasms
Neoplasms
Lung
Innate Immunity
Up-Regulation

Keywords

  • CCL2
  • CCR2
  • Immune effector monocytes
  • Metastatic breast cancer
  • STING

ASJC Scopus subject areas

  • General

Cite this

Immune effector monocyte–neutrophil cooperation induced by the primary tumor prevents metastatic progression of breast cancer. / Hagerling, Catharina; Gonzalez, Hugo; Salari, Kiarash; Wang, Chih Yang; Lin, Charlene; Robles, Isabella; van Gogh, Merel; Dejmek, Annika; Jirström, Karin; Werb, Zena.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 116, No. 43, 22.10.2019, p. 21704-21714.

Research output: Contribution to journalArticle

Hagerling, Catharina ; Gonzalez, Hugo ; Salari, Kiarash ; Wang, Chih Yang ; Lin, Charlene ; Robles, Isabella ; van Gogh, Merel ; Dejmek, Annika ; Jirström, Karin ; Werb, Zena. / Immune effector monocyte–neutrophil cooperation induced by the primary tumor prevents metastatic progression of breast cancer. In: Proceedings of the National Academy of Sciences of the United States of America. 2019 ; Vol. 116, No. 43. pp. 21704-21714.
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