CSF1R and metastatic neoplasm: Taking into consideration our findings that CSF-1 signaling is critical for the recruitment of tumor cell-macrophage pairs to the blood vessels in the primary tumor, the transient opening of the blood vessels at TMEM doorways (Fig. 4B), and intravasation of tumor cells at TMEM doorways (Figs. 4D and 5E), we expect that treating patients with CSF-1R inhibitors would be efficacious in preventing tumor cell dissemination, metastatic disease and therefore reducing metastatic burden, though not necessarily in preventing primary tumor growth.