Objective:

To summarize the biological basis, clinical progress, and challenges of TCR-T therapy in treating solid tumors, highlighting its significance compared to existing treatments.

Key Findings:

• TCR-T therapy can recognize intracellular antigens, extending targetability beyond cell-surface proteins.
• Clinical activity is inconsistent due to HLA restriction, heterogeneous antigen expression, and an immunosuppressive tumor microenvironment, necessitating improved antigen presentation and T-cell fitness.
• Durable tumor control requires not only target recognition but also effective antigen presentation and T-cell fitness.

Interpretation:

TCR-T therapy offers a promising framework for solid tumor treatment, but its efficacy is limited by biological and environmental challenges, including HLA restriction and tumor microenvironment factors.

Limitations:

• HLA restriction limits the applicability of TCR-T therapy.
• Antigen presentation can be unstable, affecting therapeutic outcomes.
• The tumor microenvironment can suppress T-cell function and trafficking, highlighting the need for ongoing research.

Conclusion:

Broader and more durable benefits from TCR-T therapy will require integrated advances in target selection, safety design, and cellular engineering, addressing the identified challenges.