Trained immunity in cancer and autoimmunity: a double-edged sword in immune memory reprogramming

Area of Science:

• Immunology
• Epigenetics
• Metabolic pathways

Background:

• Trained immunity involves long-term innate immune cell reprogramming via epigenetic and metabolic changes.
• It bridges innate and adaptive immunity, playing a dual role in disease.

Purpose of the Study:

• To review the mechanisms, roles, and therapeutic strategies of trained immunity in cancer and autoimmune diseases.
• To explore future directions in trained immunity research and application.

Main Methods:

• Review of existing literature on trained immunity mechanisms, including histone modifications, metabolic pathways (glycolysis, mTOR/HIF-1α), and key regulators (NOD2, PRRs).
• Analysis of trained immunity's role in antitumor responses and its contribution to autoimmune diseases (rheumatoid arthritis, lupus, multiple sclerosis).
• Examination of therapeutic strategies (small molecules, β-glucan, statins, BCG derivatives) and future directions (vaccines, AI integration).

Main Results:

• Trained immunity enhances antitumor responses by boosting innate cell cytotoxicity and remodeling the tumor microenvironment.
• Maladaptive trained immunity, induced by infections or dysbiosis, can lead to hyperinflammation and exacerbate autoimmune conditions.
• Therapeutic modulation of trained immunity shows potential for cancer immunotherapy and autoimmunity control, despite risks of unintended immune activation.

Conclusions:

• Trained immunity presents a complex interplay between cancer and autoimmunity, offering therapeutic targets.
• Understanding and modulating trained immunity is crucial for developing innovative treatments.
• Future research should focus on personalized interventions and integrating advanced technologies like AI.