Small molecular drugs reshape tumor microenvironment to synergize with immunotherapy

Area of Science:

• Immunology
• Oncology
• Pharmacology

Background:

• Immune checkpoint blockade (ICB) therapy, including anti-programmed death 1 (anti-PD-1) and anti-programmed death-ligand 1 (anti-PD-L1), is a promising cancer treatment.
• A significant challenge is the limited response rate, often due to an immunosuppressive tumor microenvironment (TME).
• The TME exhibits diminished innate immune sensing and elevated immunosuppressive factors, hindering adaptive immunity and immunotherapy efficacy.

Purpose of the Study:

• To review small molecule drugs that can synergize with ICB therapy, particularly anti-PD-1/anti-PD-L1 treatments.
• To explore therapeutic strategies for reversing resistance to ICB by targeting the TME.
• To highlight how these drugs can restore innate sensing and reduce immunosuppression within the TME.

Main Methods:

• Literature review of current small molecular drugs.
• Analysis of drug mechanisms in combination with immunotherapy.
• Focus on drugs that modulate the tumor microenvironment.

Main Results:

• Small molecule drugs show potential to enhance the efficacy of anti-PD-1/anti-PD-L1 therapies.
• These drugs can counteract TME-mediated resistance by restoring innate immune sensing.
• Selected small molecules can effectively limit the production or activity of immunosuppressive factors within the TME.

Conclusions:

• Combining small molecule drugs with ICB therapy offers a viable strategy to improve patient response rates.
• Targeting innate sensing and immunosuppressive factors in the TME is crucial for overcoming ICB resistance.
• Further research into these synergistic combinations holds promise for advancing cancer immunotherapy.