期刊
SCIENTIFIC REPORTS
卷 7, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/srep45593
关键词
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资金
- USPHS [R01 CA134799]
- Harry J. Lloyd Charitable Trust
- Joanna M. Nicolay Melanoma Foundation (EC-T)
- Dartmouth Immunology Training Grant [USPHS T32 AI07363]
- Cancer Center [USPHS P30 CA02310836]
- Dartmouth Immunology COBRE [USPHS P30 GM103415-14]
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/macro phage 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 antitumor 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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