HLA molecules: Another challenge for CAR T cell therapy

CAR-T cell therapy marks a groundbreaking advancement in the treatment of hematological malignancies, demonstrating significant potential to induce durable remissions. However, several limitations hinder its effectiveness, including antigen loss, immune evasion, and hostile tumor microenvironment. The interplay between CAR-T cell therapy and HLA molecules, particularly HLA-DR and HLA-G, emphasises critical challenges to achieving sustained therapeutic success. Monocytes with low or negative HLA-DR expression and high HLA-G presence contribute to immune evasion and reduced CAR-T cell effectiveness. Additionally, genetic variations in HLA influence susceptibility to hematological malignancies and disease progression. Therapeutic strategies to regulate HLA expression and function are crucial to overcome these obstacles. Approaches such as blocking HLA-G, enhancing HLA-DR expression, and optimising HLA profiles in patients by gene editing can improve outcomes of CAR-T cell therapy. Continued research on HLA-mediated immune modulation will improve these strategies and advance CAR-T cell therapy.