Immune Effector Monocyte–Neutrophil Cooperation Induced by the Primary Tumor Prevents Metastatic Progression of Breast Cancer
Immune effector monocyte–neutrophil cooperation induced by the primary tumor prevents metastatic progression of breast cancer Catharina Hagerlinga,b,1,2, Hugo Gonzaleza,3, Kiarash Salaria,3, Chih-Yang Wanga,4, Charlene Lina, Isabella Roblesa, Merel van Gogha, Annika Dejmekc, Karin Jirströmb, and Zena Werba,d,2 aDepartment of Anatomy, University of California, San Francisco, CA 94143-0452; bDepartment of Clinical Sciences, Division of Clinical Oncology and Pathology, Lund University, SE-221 85 Lund, Sweden; cDepartment of Translational Medicine, Lund University, Malmö SUS, SE-214 21 Malmö, Sweden; and dHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94143 Contributed by Zena Werb, August 30, 2019 (sent for review May 3, 2019; reviewed by Yves DeClerck and Mikala Egeblad) Metastatic behavior varies significantly among breast cancers. Mech- patients’ breast cancer tumors and is hence an attractive preclinical anisms explaining why the majorityofbreastcancerpatientsnever model to find novel therapeutic alternatives for metastatic breast develop metastatic outgrowth are largely lacking but could underlie cancer (12). We furthermore validated our PDX-derived findings the development of novel immunotherapeutic target molecules. Here with a large primary breast cancer tissue microarray (TMA), pleural we show interplay between nonmetastatic primary breast cancer effusions from breast cancer patients and an immunocompetent and innate immune response, acting together to control metastatic syngeneic mammary cancer model. Taken together, we reveal in- progression. The primary tumor systemically recruits IFNγ-producing terplay between the primary breast cancer tumor and myeloid im- immune effector monocytes to the lung. IFNγ up-regulates Tmem173/ mune response, acting together to control metastatic progression.
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