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

Sci Rep. 2017 Mar 30:7:45593. doi: 10.1038/srep45593.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Lung Neoplasms / immunology*
  • Lung Neoplasms / secondary*
  • Macrophages / immunology*
  • Melanoma / immunology
  • Melanoma / pathology*
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Monocytes / immunology*
  • Neoplasm Metastasis / immunology
  • Receptors, CXCR3 / genetics
  • Receptors, CXCR3 / immunology*
  • Signal Transduction

Substances

  • Cxcr3 protein, mouse
  • Receptors, CXCR3