title: CXCR3+monocytes/macrophages are required for establishment of pulmonary metastases.
abstract: We present a new foundational role for CXCR3+monocytes/macrophages in the process of tumor engraftment in the lung. CXCR3 is associated with monocytic and lymphocytic infiltration of inflamed or tumor-bearing lung. Although the requirement for tumor-expressed CXCR3 in metastatic engraftment has been demonstrated, the role of monocyte-expressed CXCR3 had not been appreciated. In a murine model of metastatic-like melanoma, engraftment was coordinate with CXCR3+monocyte/macrophage accumulation in the lungs and was sensitive to pharmacologic inhibition of CXCR3 signaling. Tumor engraftment to lung was impaired in CXCR3-/-mice, and transient reconstitution with circulating CXCR3-replete monocytes was sufficient to restore engraftment. These data illustrate the paradoxical pro-tumor role for CXCR3 in lung immunobiology wherein the CXCR3 axis drives both the anti-tumor effector cell chemoattraction and pro-tumor infiltration of the lungs and suggests a potential therapeutic target for lung-tropic metastasizing cancers.
authors.affiliation: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth College, Lebanon, NH 03756.
authors.forename: Kiah L
authors.initials: KL
authors.lastname: Butler
authors.affiliation: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth College, Lebanon, NH 03756.
authors.forename: Eleanor
authors.initials: E
authors.lastname: Clancy-Thompson
authors.affiliation: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth College, Lebanon, NH 03756.|Department of Medical Education, Geisel School of Medicine at Dartmouth College, Hanover, NH 03755, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Mullins
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D008175:Lung Neoplasms / Q000276:immunology* / Q000556:secondary*; D008264:Macrophages / Q000276:immunology*; D008545:Melanoma / Q000276:immunology / Q000473:pathology*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology*; D009362:Neoplasm Metastasis / Q000276:immunology; D054367:Receptors, CXCR3 / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction
chemical_list: C515188:Cxcr3 protein, mouse; D054367:Receptors, CXCR3