@article{719583b3f1ea4aaabcabe425e6890aaf,
title = "Immune effector monocyte–neutrophil cooperation induced by the primary tumor prevents metastatic progression of breast cancer",
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.",
keywords = "CCL2, CCR2, Immune effector monocytes, Metastatic breast cancer, STING",
author = "Catharina Hagerling and Hugo Gonzalez and Kiarash Salari and Wang, {Chih Yang} and Charlene Lin and Isabella Robles and {van Gogh}, Merel and Annika Dejmek and Karin Jirstr{\"o}m and Zena Werb",
note = "Funding Information: ACKNOWLEDGMENTS. We thank Elena Atamanuic, Vaishnavi Sitarama, and Elizabeth Willey for their help with the in vivo PDX studies; Bj{\"o}rn Nodin for immunohistochemical staining of the breast cancer TMA; Kristina Ekstr{\"o}m-Holka for immunohistochemical staining of the pleural effusions; Dr. Jason Rock for the CCR2KO Balb/c mouse strain; and Carl Hagerling for help with the drawing of the illustrations. This study was supported by grants from the National Cancer Institute (CA057621, CA180039, CA199315, and CA190851 to Z.W.); the Parker Institute for Immunotherapy (to Z.W.); by funds from the Tegger Foundation, Wenner-Gren Foundations, Sweden-America Foundation, Swedish Society of Medicine, Maggie Stephens, L{\"a}kares{\"a}llskapet i Lund, and Swedish Society for Medical Research (to C.H.); by a Becas Chile Scholarship (to H.G.); and by the Taiwan Ministry of Science and Technology Grant MOST104-2917-I-006-002 (to C.-Y.W.). Funding Information: We thank Elena Atamanuic, Vaishnavi Sitarama, and Elizabeth Willey for their help with the in vivo PDX studies; Bj{\"o}rn Nodin for immunohistochemical staining of the breast cancer TMA; Kristina Ekstr{\"o}m-Holka for immunohistochemical staining of the pleural effusions; Dr. Jason Rock for the CCR2KO Balb/c mouse strain; and Carl Hagerling for help with the drawing of the illustrations. This study was supported by grants from the National Cancer Institute (CA057621, CA180039, CA199315, and CA190851 to Z.W.); the Parker Institute for Immunotherapy (to Z.W.); by funds from the Tegger Foundation, Wenner-Gren Foundations, Sweden-America Foundation, Swedish Society of Medicine, Maggie Stephens, L{\"a}kares{\"a}llskapet i Lund, and Swedish Society for Medical Research (to C.H.); by a Becas Chile Scholarship (to H.G.); and by the Taiwan Ministry of Science and Technology Grant MOST104-2917-I-006-002 (to C.-Y.W.). Publisher Copyright: {\textcopyright} 2019 National Academy of Sciences. All rights reserved.",
year = "2019",
month = oct,
day = "22",
doi = "10.1073/pnas.1907660116",
language = "English",
volume = "116",
pages = "21704--21714",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "43",
}
