Human leukocyte antigen class I (HLA-I) (HLA-I)

Human leukocyte antigen class I (HLA-I) molecules are critical cell-surface glycoproteins that present intracellularly derived peptides to CD8+ cytotoxic T lymphocytes (CTLs), facilitating the immune system's ability to identify and eliminate malignant or infected cells (UniProt). In neuroblastoma, HLA-I expression is characteristically low or absent, a phenomenon known as "immune escape" that prevents CTL-mediated tumor clearance (PubMed: 15833823). This downregulation is frequently linked to the amplification of the MYCN oncogene and transcriptional silencing of components in the antigen processing machinery, such as TAP1 and tapasin (PubMed: 22431872). Therapeutic interventions aim to reverse this silencing using pro-inflammatory cytokines like Interferon-gamma or epigenetic agents such as histone deacetylase (HDAC) inhibitors to restore HLA-I surface density and enhance the efficacy of T-cell-based immunotherapies (PubMed: 31534003). Additionally, the lack of HLA-I on neuroblastoma cells makes them primary targets for natural killer (NK) cells, which are regulated by "missing-self" recognition, offering an alternative therapeutic strategy for HLA-deficient tumors (PubMed: 15634879).

Other names

MHC class IMajor histocompatibility complex class IHLA-AHLA-BHLA-C

Pharmacological induction of HLA class I expression on the surface of neuroblastoma cells to restore antigen presentation and enhance recognition by cytotoxic T lymphocytes (CTLs).