NK 细胞还是自然调节细胞？NK 细胞在检查点免疫治疗中的双重作用

Natural killer (NK) cells have long been recognized as central antitumor effectors capable of eliminating transformed cells without prior sensitization.

However, recent studies reveal a more nuanced reality: NK cells can also act as regulators that hinder CD8⁺ T-cell immunity and blunt the efficacy of immune checkpoint blockade (ICB). Two back-to-back in Cancer Discovery provide compelling mechanistic insights. Pozniak et al. demonstrate that cytotoxic NK cells accumulate in immune-excluded melanoma, where they are recruited via CX3CR1 and prevent CD8⁺ T-cell infiltration, thereby limiting responses to anti-PD-1 therapy. In parallel, Song et al.

show that (TANKs) cells compete with CD8⁺ T cells for IL-2 and type I interferons (IFN-I; mainly IFN-α/β), disrupting effector differentiation and reducing ICB sensitivity. Collectively, these findings underscore the dual nature of NK cells as both killers and regulators whose context-dependent activity can either amplify or suppress antitumor immunity.

Therapeutically, strategies to deplete, block, or reprogram suppressive NK subsets while preserving their cytotoxic and dendritic cell (DC)-recruiting functions may help overcome resistance and enhance the durability of checkpoint blockade.