Lung metastases from an orthotopic syngeneic breast cancer (left, wild type; right, knockout) are shown. The study found that metastases are highly reduced in CD81-deficient mice. Immune suppressor cells, T-regulatory (Treg) cells, and myeloid-derived suppressor cells were impaired in these knockout mice. Wild-type Tregs restored the metastatic phenotype in the knockout animals. For details, see article by Vences-Catalán and colleagues on page 4517.