A synthetic biomaterial scaffold, like the poly(ε-caprolactone) scaffold shown on the cover, can function as a synthetic metastatic niche to reveal the nature of early distant metastases. Following implantation, these scaffolds promote tissue ingrowth, which upon cancer initiation is transformed into a metastatic niche that captures aggressive metastatic tumor cells. An immune signature was generated from gene expression analysis of the niche cells, which consists of immune, stromal, and tumor cells. In breast cancer models, this signature tracked the progression of metastatic conditioning and regression of disease following therapy and differentiated the therapeutic responders and non-responders. Acknowledgement to Angelica R. Galvan for SEM image capture. For details, see article by Oakes and colleagues on page 602.