The Immune Microenvironment in Liver Cancer: From Analysis to Targeting

Area of Science:

• Oncology
• Nanotechnology
• Immunology

Background:

• Liver cancer (LC) recurrence is high due to its immunosuppressive tumor microenvironment (TME).
• Advanced LC stages have poor prognosis despite treatment advancements.
• Nanomedicines (NMs) present novel strategies for TME modulation in LC.

Purpose of the Study:

• To systematically analyze mechanisms of immunosuppressive TME formation in LC.
• To explore the potential of smart responsive NMs in targeted delivery, immune remodeling, and multimodal therapy for LC.

Main Methods:

• Review of literature on LC immunosuppressive TME mechanisms.
• Analysis of smart responsive NMs for targeted delivery (passive and active) and spatiotemporal drug release.
• Exploration of NM-mediated reprogramming of TME components and functions.

Main Results:

• LC TME involves abnormal physiology, ECM deposition, immune cell dysfunction, metabolic changes, and microbiota influences.
• Smart NMs overcome delivery barriers, targeting LC cells and immunosuppressive cells.
• NMs enable precise drug release for integrated chemo-, immuno-, and physical therapies, reprogramming the TME.

Conclusions:

• Smart NMs offer a paradigm shift for LC therapy via targeted delivery and immune reprogramming.
• NMs can remodel TME by altering physiological conditions, inhibiting ECM, regulating metabolism, and modulating microbiota.
• Further optimization for toxicity and clinical translation is needed for smart NMs in LC treatment.