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  3. Association between human leukocyte antigen E expression and outcomes in solid tumors: a systematic review and meta-analysis

Association between human leukocyte antigen E expression and outcomes in solid tumors: a systematic review and meta-analysis

  • Front Oncol. 2025 Feb 24:15:1525924. doi: 10.3389/fonc.2025.1525924.
Javier David Benitez Fuentes 1,  Jorge Bartolome Arcilla 2 3,  Antonio David Lazaro Sanchez 4,  Alicia de Luna Aguilar 5,  Kauzar Mohamed Mohamed 6,  Kissy Guevara-Hoyer 6 7,  Pablo Ballestin Martinez 8,  Miguel Borregon Rivilla 1,  Asia Ferrandez Arias 1,  Silvia Sánchez-Ramon 6 7,  Alberto Ocaña 2 3 9
Affiliations

Affiliations

  • 1 Department of Medical Oncology, Elche General University Hospital, Alicante, Spain.
  • 2 Department of Medical Oncology, Hospital Clinico San Carlos, Instituto de Investigación Sanitaria San Carlos (IdISSC), and CIBERONC, Madrid, Spain.
  • 3 Experimental Therapeutics in Cancer Unit, Instituto de Investigación Sanitaria San Carlos (IdISSC), Madrid, Spain.
  • 4 Department of Medical Oncology, Santa Lucia General University Hospital, Cartagena, Spain.
  • 5 Department of Medical Oncology, Hospital General Universitario Morales Meseguer, Murcia, Spain.
  • 6 Department of Immunology, IML and IdISSC, Hospital Clinico San Carlos, Madrid, Spain.
  • 7 Department of Immunology, Ophthalmology and ENT, School of Medicine, Complutense University, Madrid, Spain.
  • 8 Department of Medical Oncology, Hospital 12 de Octubre, Madrid, Spain.
  • 9 START Madrid-Fundación Jiménez Díaz (FJD) Early Phase Program, Fundación Jiménez Díaz Hospital, Madrid, Spain.
PMID: 40066089 DOI: 10.3389/fonc.2025.1525924
Abstract

Background: Immunotherapy has gained momentum with the discovery of novel antibodies targeting immunosuppressive proteins. HLA-E, a non-classical major histocompatibility complex class I (MHC-I) protein, exhibits immunosuppressive properties, potentially influencing tumor immune evasion mechanisms. The association between Human Leukocyte Antigen E (HLA-E) expression and outcomes in solid tumors remains unclear.

Methods: A systematic review of MEDLINE, Scopus, and the Cochrane Library up to March 15, 2024, was conducted following the PRISMA guidelines. Studies investigating HLA-E expression in solid tumors and its association with OS and DFS were included. Statistical analysis was performed using Comprehensive Meta-Analysis (version 3.0) with random-effects models.

Results: After screening 657 articles, 11 studies were included, comprising a total of 1781 patients. The studies encompassed a variety of Cancer types, follow-up periods, and staging details, with the majority focusing on non-metastatic cases. Notably, three studies evaluated colorectal Cancer, while Others focused on pancreatic, esophageal, brain, renal cell, gastric, endometrial, cervical, and hepatocellular carcinomas. The mean age of the patients was 59.81 ± 2.01 years, and the median follow-up period was 57.45 ± 8.91 months. HLA-E expression demonstrated no statistically significant association with OS (HR 0.913, 95% CI = 0.567-1.469; P=0.707), with significant heterogeneity observed (I2 = 84%). However, HLA-E non-expression was significantly associated with improved DFS (HR 1.406, 95% CI = 1.027-1.930; P=0.03), with moderate heterogeneity (I2 = 45%).

Conclusion: This systematic review highlights that HLA-E expression in solid tumors could be a biomarker of better prognosis, measured by DFS. These findings align with the clinical benefit observed for agents targeting this pathway. However, further studies should be performed to confirm these preliminary observations.

Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024527598, identifier CRD42024527598.

Keywords

HLA-E; cancer; human leukocyte antigen; immunotherapy; solid tumors; survival.

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