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

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.