| First Author | Im K | Year | 2023 |
| Journal | Biochem Biophys Res Commun | Volume | 680 |
| Pages | 7-14 | PubMed ID | 37703603 |
| Mgi Jnum | J:344269 | Mgi Id | MGI:7538609 |
| Doi | 10.1016/j.bbrc.2023.09.021 | Citation | Im K, et al. (2023) AXL receptor tyrosine kinase inhibition improves the anti-tumor effects of CD8(+) T cells by inducing CD103(+) dendritic cell-mediated T cell priming. Biochem Biophys Res Commun 680:7-14 |
| abstractText | 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). |
