Although immune checkpoint inhibition (ICI) has revolutionized the treatment of advanced melanoma, reliable predictive biomarkers are still lacking. In this issue of Cancer Research, Antoranz and colleagues used RNA sequencing and multiplexed IHC to study the spatial immune landscape of pretreatment melanoma specimens from patients who either responded or did not respond to antiprogrammed death protein 1 (PD-1) therapy. The authors identified the spatial interaction between cytotoxic T cells and M1-like macrophages expressing PD-L1 at the tumor boundary as predictive of responses to immune checkpoint inhibition. These studies pave the way for the development of new spatial biomarkers to identify patients most likely to benefit from ICI therapy. See related article by Antoranz et al., p. 3275.