Cancer cells are known to secrete exosomes with pro-metastatic effects. Pancreatic-cancer-derived exosomes are now shown to promote liver metastasis by eliciting pre-metastatic niche formation through a multi-step process. This involves uptake of exosome-derived factors by liver Kupffer cells and hepatic stellate cell activation to generate a fibrotic microenvironment with immune cell infiltrates that favours metastasis.