Natural killer cells in colorectal cancer liver metastasis: redefining immune surveillance and plasticity

Natural killer (NK) cells are key effectors in innate immunity and serve as early responders against disseminated tumor cells. In colorectal cancer liver metastasis (CRLM), the liver’s unique immune landscape presents both challenges and opportunities for NK cell–mediated tumor control. While NK cells have long been considered uniform cytotoxic sentinels, recent studies have reshaped this view by uncovering a diverse spectrum of NK cell states with distinct migratory, transcriptional, and functional programs. These findings reveal a heterogeneous NK-cell compartment in the metastatic liver shaped by tissue context and microenvironmental cues, with distinct residency-associated and functional programs. Advances in high-dimensional single-cell technologies have accelerated the characterization of NK cell heterogeneity, plasticity, and interactions within the metastatic niche. In this review, we summarize recent insights into the evolving roles of NK cells in CRLM, highlighting how they contribute to immune surveillance, niche remodeling, and potential therapeutic modulation.