Immune effector monocyte–neutrophil cooperation induced by the primary tumor prevents metastatic progression of breast cancer
(2019) In Proceedings of the National Academy of Sciences of the United States of America 116(43). p.21704-21714- 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... (More)
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.
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- author
- Hagerling, Catharina LU ; Gonzalez, Hugo ; Salari, Kiarash ; Wang, Chih Yang ; Lin, Charlene ; Robles, Isabella ; van Gogh, Merel ; Dejmek, Annika LU ; Jirström, Karin LU and Werb, Zena
- organization
- publishing date
- 2019
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- CCL2, CCR2, Immune effector monocytes, Metastatic breast cancer, STING
- in
- Proceedings of the National Academy of Sciences of the United States of America
- volume
- 116
- issue
- 43
- pages
- 11 pages
- publisher
- National Academy of Sciences
- external identifiers
-
- scopus:85073708969
- pmid:31591235
- ISSN
- 0027-8424
- DOI
- 10.1073/pnas.1907660116
- language
- English
- LU publication?
- yes
- id
- 3e20ebd5-85be-4368-9b5b-d81e57f2fd93
- date added to LUP
- 2019-10-30 08:06:35
- date last changed
- 2024-09-18 12:20:37
@article{3e20ebd5-85be-4368-9b5b-d81e57f2fd93, abstract = {{<p>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.</p>}}, author = {{Hagerling, Catharina and Gonzalez, Hugo and Salari, Kiarash and Wang, Chih Yang and Lin, Charlene and Robles, Isabella and van Gogh, Merel and Dejmek, Annika and Jirström, Karin and Werb, Zena}}, issn = {{0027-8424}}, keywords = {{CCL2; CCR2; Immune effector monocytes; Metastatic breast cancer; STING}}, language = {{eng}}, number = {{43}}, pages = {{21704--21714}}, publisher = {{National Academy of Sciences}}, series = {{Proceedings of the National Academy of Sciences of the United States of America}}, title = {{Immune effector monocyte–neutrophil cooperation induced by the primary tumor prevents metastatic progression of breast cancer}}, url = {{http://dx.doi.org/10.1073/pnas.1907660116}}, doi = {{10.1073/pnas.1907660116}}, volume = {{116}}, year = {{2019}}, }