SLC39-driven zinc influx orchestrates pleiotropic tumor-immune system cross-talk to establish immune suppression in colorectal cancer.

SLC39-driven zinc influx promotes immune suppression and therapy resistance in colorectal cancer by activating a tumor cell state linked to poor prognosis.

• Why it matters: Understanding how nutrient-transport systems influence tumor-immune interactions is crucial for developing strategies to overcome immune evasion and improve immunotherapy outcomes in colorectal cancer.
• What they did: Researchers integrated multi-omics, single-cell transcriptomics, spatial profiling, and functional assays on 258 patients to identify a zinc-driven immunosuppressive circuit centered on SLC39 and associated molecular pathways.
• The result: The study revealed that SLC39-mediated zinc influx activates a tumor cell program involving CD24 expression, which suppresses macrophage phagocytosis and correlates with immune exclusion and therapy resistance, with a seven-gene signature predicting immunotherapy response.