[HTML][HTML] CXCR3+ monocytes/macrophages are required for establishment of pulmonary metastases

KL Butler, E Clancy-Thompson, DW Mullins - Scientific reports, 2017 - nature.com
KL Butler, E Clancy-Thompson, DW Mullins
Scientific reports, 2017nature.com
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 …
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.
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