HLA class I and II polymorphisms in pediatric neuroblastoma: mechanistic links to immune surveillance, tumor evolution, and clinical translation
Year: 2026
Type: review
Abstract: Background: Pediatric solid tumors, including neuroblastoma (NB), emerge within an immature immune system where inherited immunogenetic variation may affect tumor onset and progression. Differences in HLA system are central to antigen presentation and immune recognition. However, their role in pediatric solid tumors is less clearly defined than in hematologic malignancies, and current evidence remains limited. Objective: This review summarizes evidence linking inherited HLA class I and II variation to NB susceptibility and clinical outcomes in pediatric NB. Tumor-associated HLA alterations, including reduced HLA expression and antigen-presentation defects that contribute to immune escape, are discussed as distinct but biologically related mechanisms. Methods: A structured synthesis of case-control and cohort studies evaluating HLA alleles, haplotypes, and expression in pediatric NB was performed. Data were organized by population, sample size, HLA locus, and association strength, and interpreted using concepts of antigen presentation, immune editing, and tumor microenvironment interactions. Results: T-cell responses and inflammatory signaling. Some associations appeared subtype-specific, particularly in MYCN-amplified tumors, although evidence stratified by stage, age, and risk group remains limited. Beyond susceptibility, specific class I variants were associated with overall survival and progression-free survival including among patients receiving anti-GD2 immunotherapy, while HLA-KIR interactions and transplantation-related immunogenetic parameters were associated with disease progression and survival following hematopoietic stem cell transplantation. Separately, tumor-associated reductions in human leukocyte antigen expression or antigen-processing capacity may facilitate immune evasion by limiting effective antitumor immune recognition, though direct evidence remains limited. Conclusion: loci, are plausible, but not fully confirmed determinants of NB susceptibility and clinical outcome, with the strongest evidence relating to OS and PFS, clinical outcomes among patients receiving anti-GD2 immunotherapy, and outcomes following stem cell transplantation.
Source: Frontiers in Genetics
Authors: Amira Daldoul, Wassim Y. Almawi
Institutions: Hospital Fatuma Bourguiba Monastir, Tunis El Manar University
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7223106872