Document Type

Article

Publication Date

3-30-2017

Publication Title

Scientific Reports

Department

Geisel School of Medicine

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.

DOI

10.1038/srep45593

Original Citation

Butler KL, Clancy-Thompson E, Mullins DW. CXCR3+ monocytes/macrophages are required for establishment of pulmonary metastases. Sci Rep. 2017 Mar 30;7:45593. doi: 10.1038/srep45593. PMID: 28358049; PMCID: PMC5372355.

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