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

被引：1

作者：

Im, Kyungtaek ^{[1
]}

Choi, Yun Jung ^{[1
]}

Kim, Dong Ha ^{[1
]}

Kim, Da -Som ^{[2
]}

Ban, Kyosun ^{[2
]}

Ji, Wonjun ^{[3
]}

Baek, In-Jeoung ^{[4
]}

Choi, Chang-Min ^{[3
]}

Lee, Jae Cheol ^{[5
]}

Rho, Jin Kyung ^{[6
,7
]}

机构：

[1] Univ Ulsan, Asan Med Ctr, Asan Inst Life Sci, Coll Med, Seoul 05505, South Korea

[2] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Biomed Sci,AMIST, Seoul 05505, South Korea

[3] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Pulmonol & Crit Care Med, Seoul 05505, South Korea

[4] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Cell & Genet Engn, Seoul 05505, South Korea

[5] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Oncol, Seoul 05505, South Korea

[6] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Biochem & Mol Biol, Seoul 05505, South Korea

[7] Univ Ulsan, Coll Med, Dept Biochem & Mol Biol, 88 Olymp Ro 43 Gil, Seoul 05505, South Korea

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2023年 / 680卷

基金：

新加坡国家研究基金会;

关键词：

AXL receptor tyrosine kinase (AXL); Dendritic cell (DC); Tumor microenvironment; Lung cancer; CD8+T cell; DENDRITIC CELLS; ACTIVATION; MACROPHAGES; EXPRESSION; RESISTANCE; RESPONSES; INVASION;

D O I：

10.1016/j.bbrc.2023.09.021

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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).

引用

页码：7 / 14

页数：8

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