Association between Human Leukocyte Antigen E Expression and Outcomes in Solid Tumors: a Systematic Review and Meta-analysis

Javier David Benitez Fuentes ^1* Jorge Bartolomé ² Antonio David Lazaro Sanchez ³ Alicia de Luna Aguilar ³ Kauzar Mohamed Mohamed ² Kissy Guevara-Hoyer ² Pablo Ballestín Martínez ² Miguel Borregón ¹ Asia Ferrandez Arias ¹ Silvia Sánchez-Ramón ² Alberto Ocaña ^2*

• ¹ Hospital General Universitario de Elche, Elche, Spain
• ² Health Research Institute of the Hospital Clínico San Carlos (IdISSC), Madrid, Madrid, Spain
• ³ Department of Hematology and Medical Oncology, Hospital General Universitario Morales Meseguer, Murcia, Murcia, Spain

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%).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.