Abstract Summary: Robust biomarkers of response that predict which patients will or will not respond to immune checkpoint blockade need to be identified. New data suggest that the presence of an adaptive immune signature in the tumor biopsies of patients with melanoma early on therapy compared to pretreatment can identify responders from nonresponders. Cancer Discov; 6(8); 818–20. ©2016 AACR. See related article by Chen et al., p. 827.