Adenosine Concentration Determination for in Vitro Tumor Microenvironment Simulation

Area of Science:

• Immunology
• Cancer Biology
• Pharmacology

Background:

• The tumor microenvironment (TME) plays a crucial role in cancer progression and immune evasion.
• Adenosine (ADO) is a key molecule within the TME, known to influence cellular functions.
• Understanding ADO's concentration-dependent effects is vital for developing effective cancer immunotherapies.

Purpose of the Study:

• To investigate the concentration-dependent effects of adenosine (ADO) on tumor cells and natural killer (NK) cells within the tumor microenvironment (TME).
• To determine the critical threshold concentration of ADO that modulates tumor immune escape mechanisms.
• To elucidate the bidirectional regulatory role of ADO in cancer and immunity.

Main Methods:

• An in vitro simulation system was utilized to assess ADO's impact.
• Evaluated ADO's effects on A549 (lung carcinoma) and A375 (melanoma) cell proliferation and migration.
• Assessed ADO's influence on NK92 cell activity, cytokine secretion (IFN-γ), and cytotoxicity against various cancer cell lines (A549, A375, HepG2).

Main Results:

• A concentration of 50 μM ADO significantly enhanced tumor cell proliferation (60%-80%) and migration (30%-40%).
• Higher ADO concentrations (>200 μM) demonstrated an inhibitory effect on tumor cells.
• ADO suppressed NK92 cell activity and IFN-γ secretion in a dose-dependent manner, reducing proliferation by 14.5% and IFN-γ by 24% at 50 μM.
• ADO impaired NK cell-mediated cytotoxicity against A549, A375, and HepG2 cells by 20.3%, 22.4%, and 31.5%, respectively.

Conclusions:

• 50 μM ADO serves as a critical threshold concentration for simulating TME effects.
• ADO exhibits concentration-dependent bidirectional regulation, promoting tumor growth at lower concentrations and potentially inhibiting it at higher ones.
• ADO significantly impairs NK cell function, contributing to tumor immune escape.