AXL receptor tyrosine kinase inhibition improves the anti-tumor effects of CD8 T cells by inducing CD103 dendritic cell-mediated T cell priming.

AXL is a member of TAM receptor family and has been highlighted as a potential target for cancer treatment. Accumulating evidence has uncovered the critical role of the AXL signaling pathway in tumor growth, metastasis, and resistance against anti-cancer drugs, as well as its association with cancer immune escape. However, the function of AXL as a manipulator of the immune system in the tumor microenvironment (TME) remains unclear. Therefore, in this study, we investigated the impact of AXL on immune cells in the TME of a syngeneic tumor model using AXL knockout (AXL) mice. Compared to AXL wild-type (AXL) mice, tumor growth was significantly suppressed in AXL mice, and an induced population of tumor-infiltrated CD8 T cells and CD103 dendritic cells (DCs) was observed. The change of CD8 T cells and CD103 DCs was also confirmed in tumor-draining lymph nodes (TdLN). In addition, the clonal expansion of OVA-specific CD8 T cells was dominant in AXL mice. Finally, anti-PD-1 treatment evidenced synergistic anti-cancer effects in AXL mice. Overall, our data indicate that AXL signaling may inhibit the clonal expansion of tumor-specific CD8 T cells through the regulation of the migration of CD8 T cells and DCs in TME. Thus, AXL may be a powerful molecular target to improve anti-cancer effects through single or combined therapy with immune checkpoint inhibitors (ICI).