Efficiently Reversing Immunotherapy Resistance in Lung Cancer by an Inhalable 2D Molybdenum Disulfide T Cell...

Area of Science:

• Nanotechnology
• Immunology
• Oncology

Background:

• Immunotherapy has transformed lung cancer treatment but faces challenges with patient response and resistance.
• Novel therapeutic strategies are crucial to improve treatment efficacy.

Purpose of the Study:

• To design and evaluate an inhalable 2D molybdenum disulfide T cell hyperactivation platform (2D MoS2-THP) for enhanced lung cancer immunotherapy.
• To leverage synergistic effects of IL2 and anti-PD1 for T cell activation and overcoming immunosuppression.

Main Methods:

• Anchoring IL2 and anti-PD1 proteins onto flexible 2D metallic molybdenum disulfide (MoS2).
• Utilizing MoS2 to induce cuproptosis in regulatory T cells (Tregs) via mitochondrial disruption and oxidative stress.
• Administering the platform via inhalation for improved intratumoral delivery.

Main Results:

• Achieved effective T cell hyperactivation through synergistic IL2 and anti-PD1 action.
• Demonstrated MoS2's role in inducing cuproptosis in Tregs, reducing immunosuppression.
• Inhalation delivery enhanced intratumoral accumulation and therapeutic potency while minimizing systemic side effects.

Conclusions:

• The inhalable 2D MoS2-THP is a "three-in-one" immunotherapy platform that robustly activates T cells.
• This approach effectively removes immunosuppressive barriers and remodels the tumor microenvironment.
• The platform shows promise in overcoming resistance to cancer immunotherapy with reduced toxicity.