摘要Human leukocyte antigen(HLA)molecules play a predominant role in cancer immunotherapy by harnessing the immune system's capacity to differentiate between healthy and malignant cells.Most human cell types express HLA class Ⅰ mol-ecules,which interact with T-cell receptors(TCRs)to activate T cells and initiate adaptive immunological responses.The efficacy of several immunotherapeutic strategies,including checkpoint inhibitors,CAR-T-cell therapy,and personalized cancer vaccines,is significantly influenced by HLA diversity and polymorphisms.Human leukocyte antigen E(HLA-E)is a non-classical major histocompatibility complex class Ⅰ(MHC-Ⅰ)protein that plays a crucial role in immune regulation.Unlike classical HLA molecules,HLA-E exhibits unique immunosuppressive properties that influence tumor immune evasion mechanisms.Recent studies have highlighted the importance of HLA-E expression in various hematological malignancies and solid tumors.HLA-E interacts with inhibitory receptors on natural killer(NK)cells and certain T-cell subsets,thereby modulating immune responses against tumor cells.The expression of HLA-E on tumor cells can lead to immune escape by inhibiting the cytotoxic activity of NK and CD8+T cells,which are critical for effective anti-tumor immunity.This review summarizes how HLA-E presents antigens,discusses recent advances in identifying HLA-E-restricted peptides,and evaluates current HLA-E-dependent and HLA-E-independent adoptive immunotherapies.Understanding the role of HLA-E in tumor immune evasion provides valuable insights for developing novel personalized cancer immunotherapies.Targeting HLA-E has the potential to increase the effectiveness of current treatments and improve patient prognosis across diverse cancer types.