T-Cell-Based Immunotherapy for Solid Tumors: Challenges, Mechanisms, and Combination Strategies
TL;DR
The biological mechanisms underlying CD8+ T-cell-mediated tumor killing are outlined and the major limitations faced by T cells in the treatment of solid tumors are explored, including a limited number of tumor-specific antigens, poor tumor infiltration capacity, an immunosuppressive microenvironment, metabolic stress, and T-cell exhaustion.
Abstract
T-cell-based immunotherapy has become a key approach in cancer treatment, based on the principle of utilizing immune cells to recognize and eliminate malignant cells. However, compared to certain hematologic malignancies, the response of solid tumors to this type of therapy remains suboptimal. This article outlines the biological mechanisms underlying CD8+ T-cell-mediated tumor killing and explores the major limitations faced by T cells in the treatment of solid tumors, including a limited number of tumor-specific antigens, poor tumor infiltration capacity, an immunosuppressive microenvironment, metabolic stress, and T-cell exhaustion. In addition, this article introduces adoptive T-cell therapy, CAR-T therapy, TCR-T therapy, and PD-1/PD-L1 immune checkpoint blockade therapy, emphasizing the importance of combination treatment strategies. The article also discusses antigen-specific systems such as the OT-I/B16-OVA model, which serve as important tools for studying T-cell killing mechanisms and immune evasion. Progress in this field will depend on enhancing the T cells’ specificity, persistence, and tumor homing ability, as well as their capacity to overcome inhibitory mechanisms, while ensuring clinical safety.