AXL是TAM受体家族的成员，并被认为是癌症治疗的潜在靶点。积累的证据揭示了AXL信号通路在肿瘤生长、转移和抗癌药物抵抗中的关键作用，以及其与癌症免疫逃逸的关联。然而，作为肿瘤微环境(TME)中免疫系统的调控因子，AXL的功能仍然不清楚。因此，在这项研究中，我们使用AXL基因敲除(AXL-/-)小鼠模型，调查了AXL对TME中免疫细胞的影响。与AXL野生型(AXL+/+)小鼠相比，AXL-/-小鼠中肿瘤生长显著抑制，并观察到一类充足的肿瘤浸润CD8+ T细胞和CD103+ 树突状细胞(DCs)。CD8+ T细胞和CD103+ DCs在肿瘤引流淋巴结(TdLN)中的变化也得到了确认。此外，在AXL-/-小鼠中，OVA特异性CD8+ T细胞的克隆扩张占主导地位。最后，抗-PD-1治疗在AXL-/-小鼠中显示出协同的抗癌效果。总体而言，我们的数据表明AXL信号通路可能通过调节CD8+ T细胞和DCs的迁移来抑制肿瘤特异性CD8+ T细胞的克隆扩张。因此，AXL可能是一个强有力的分子靶点，可以通过单独或联合免疫检查点抑制剂(ICIs)治疗来改善抗癌效果。Copyright © 2023 Elsevier Inc. All rights reserved.

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).Copyright © 2023 Elsevier Inc. All rights reserved.