Immune Evasion Mechanism and AXL

Area of Science:

• Oncology
• Immunology
• Molecular Biology

Background:

• Cancer immunotherapy, including CTLA-4 and PD-1/PD-L1 checkpoint inhibitors, has garnered significant interest.
• AXL receptor tyrosine kinase is implicated in cancer progression and therapeutic resistance across various cancer types.
• The GAS6/AXL pathway is frequently activated in cancer cells, driving tumor growth, survival, and immune evasion.

Purpose of the Study:

• To review the role of the GAS6/AXL signaling pathway in establishing an immunosuppressive tumor microenvironment.
• To explore how GAS6/AXL signaling contributes to immune evasion mechanisms, including T-cell exclusion and regulatory T-cell activity.
• To discuss the therapeutic potential of targeting the GAS6/AXL pathway in cancer treatment.

Main Methods:

• Literature review of preclinical and clinical studies on the GAS6/AXL pathway in cancer.
• Analysis of the molecular mechanisms by which GAS6/AXL influences tumor microenvironment composition and immune cell function.
• Synthesis of information regarding targeted therapies against AXL.

Main Results:

• The GAS6/AXL pathway actively promotes an immunosuppressive tumor microenvironment, fostering cancer cell proliferation, survival, migration, invasion, and angiogenesis.
• GAS6/AXL signaling contributes to immune evasion by regulating tumor microenvironment composition and promoting T-cell exclusion.
• The pathway negatively impacts antitumor immune responses, including NK cell activation and tumor-specific immunity.

Conclusions:

• The GAS6/AXL pathway is a critical mediator of immune evasion and a promising therapeutic target in oncology.
• Targeting GAS6/AXL may enhance the efficacy of existing immunotherapies, such as PD-1/PD-L1 inhibitors.
• Further development of selective and non-selective AXL inhibitors is warranted for multiple cancer types.