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.
Sci Rep. 2017 Mar 30;7:45593. doi: 10.1038/srep45593.
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.
我们提出了 CXCR3 单核细胞/巨噬细胞在肿瘤在肺部定植过程中的新的基础作用。CXCR3 与炎症或肿瘤肺部的单核细胞和淋巴细胞浸润有关。虽然已经证明了肿瘤表达的 CXCR3 在转移性定植中的作用,但单核细胞表达的 CXCR3 的作用尚未被认识。在转移性黑色素瘤的小鼠模型中,定植与 CXCR3 单核细胞/巨噬细胞在肺部的积累协调一致,并且对 CXCR3 信号转导的药物抑制敏感。在 CXCR3 小鼠中,肿瘤定植到肺部受损,并且循环中 CXCR3 丰富的单核细胞的短暂再构成足以恢复定植。这些数据说明了 CXCR3 在肺部免疫生物学中具有矛盾的促肿瘤作用,其中 CXCR3 轴既驱动抗肿瘤效应细胞趋化性,又促进肿瘤浸润肺部,并为肺转移癌提供了一个潜在的治疗靶点。