Pelvic lymph nodes are the most frequent sites of prostate cancer dissemination, as depicted here by pan-cytokeratin immunohistochemistry on a human specimen. However, there is little knowledge about how precociously disseminated cancer cells seed lymph nodes and protect themselves from immune surveillance. Jachetti and colleagues report that early-disseminating cancer stem-like cells seed quiescent future sites of metastasis in tumor-draining lymph nodes by engaging Tenascin-C, a protumorigenic extracellular matrix protein, which mediates local immune escape by arresting T lymphocyte activation. For details, see article by Jachetti and colleagues on page 2095.