Regression-Associated Macrophages Recruit Natural Killer Cells That Constrain Targeted Therapy Resistance.

Regression-associated macrophages promote NK cell recruitment via CCR2/5 signaling, constraining targeted therapy resistance in melanoma models.

• Why it matters: Understanding innate immune mechanisms that sustain tumor response to kinase inhibitors is crucial for improving therapy durability and overcoming resistance.
• What they did: The study analyzed immunocompetent melanoma models, identifying a macrophage subset (F4/80hiCCL5^a^MHCII^a^CD63^a^) that recruits NK cells, and used genetic and pharmacologic approaches to modulate macrophages and NK infiltration.
• The result: Restoring NK cell recruitment delayed resistance onset and analysis of patient datasets linked NK dynamics to clinical outcomes, highlighting innate immune remodeling as a target to extend therapy responses.