Axl inhibition on dendritic cells enhances STING anticancer therapy through type I interferon signaling

The Axl receptor tyrosine kinase is pivotal for metastatic tumor progression, tumor immune evasion, and regulating inflammation of innate immune cells. In this study we investigated Axl’s immune function in immunogenic tumors and found that Axl knockout (KO) mice exhibited a significant delay in tumor growth. Single-cell RNA sequencing revealed that Axl deficiency increases CD8 T cell activity. Tumor growth delay was dependent on CD8 T cells and BATF3 expression, indicating a role for Axl in regulating dendritic cell (DC) cross priming activities. Cre-driven conditional KO models further demonstrated that loss of Axl on DCs—but not on macrophages—was sufficient to slow tumor growth, a process reliant on type I interferon (IFN) signaling. Given Axl’s role in modulating IFN-I signaling, we discovered that its absence enhanced the effectiveness of STING agonists and improved the cross-priming capacity of both cDC1 and cDC2 subsets.