Fig. 4

Tumor cell-induced formation of the pre-metastatic niche. Tumor-derived EVs (miR-200b-3p, Lin28B) and tumor-derived secreted factors (TDSFs) (CXCL12, GM-CSF, IL-8) enter the metastatic target organ through the circulation. These factors produce an inhibitory effect on cytotoxic T lymphocytes mediated by tumor-infiltrating neutrophils, leading to the formation of a receptive microenvironment in the target organ including the bone and the lung for the cancer cells prior to their arrival