Immune Evasion Through Human Leukocyte Antigen Implications and Its Impact on Targeted Therapy

The malfunctioning of human leukocyte antigen (HLA) class I antigens has a substantial negative impact on the effectiveness of leukemia treatment, particularly in the development of immunotherapies that rely on T-cell activation. HLA-G, a molecule that suppresses the immune response, plays a role in repressing the activation and proliferation of T cells, natural killer cells, and antigen-presenting cells. The expression of HLA-G is associated with various pathological conditions. Tumor cells exploit the immune evasion capabilities of HLA, allowing them to evade detection and elimination by the immune system. Understanding and modifying the HLA molecules is crucial for the advancement of innovative immunotherapies targeting chronic lymphocytic leukemia. Numerous mechanisms have been investigated to elucidate how HLA facilitates tumor evasion in patients with chronic lymphocytic leukemia and other malignancies. These mechanisms include inhibiting immune cell cytolysis, altering cytokine production levels, promoting immune cell programmed cell death, and impairing chemotaxis. This review provides a comprehensive overview of immune evasion mediated by HLA and its implications for targeted therapy.