A pan-cancer single-cell atlas reported that immunotherapy-relevant macrophage crosstalk varies by sex, identifying sex-biased SPP1+ macrophage interactions linked to how tumors respond to treatment. By mapping cell states at single-cell resolution across cancers, the work provides a mechanistic hypothesis for observed clinical differences—namely that immune microenvironments may generate distinct suppressive signals depending on sex. For immuno-oncology development, the atlas offers a candidate biomarker direction (SPP1+ macrophage patterns) for refining response predictions and potentially tailoring trial stratification.