HLA-Shuttle: A system for enhancing antigen presentation in immunologically cold tumors

2026/01/01 by Daniel Hwang, Molly C. Erdman, Santosh Adhikari +18 · 1 voice
Immunology and Microbiology · Biochemistry, Genetics and Molecular Biology · Medicine · #Immunotherapy and Immune Responses #vaccines and immunoinformatics approaches #CAR-T cell therapy research

paper · doi:10.1126/sciadv.aeb0821

openalex publication_date 2026/01/01 · openalex created_date 2026/01/01 · openalex updated_date 2026/07/27

Abstract

Epitopic peptides presented by class-I human leukocyte antigen (HLA-I) proteins provide the basis of immune surveillance by T cells. Conversely, reduced surface HLA-I expression is a hallmark of immune evasion by latent viral infections and cancer, which confounds the identification of peptide antigens and neoantigens. Here, we outline a system (HLA-Shuttle) for in vitro manipulation of cells with engineered components of the HLA-I processing machinery to confer a continuum of chaperoning activity throughout their trafficking pathway. HLA-Shuttle restores antigen presentation in immunologically cold neuroblastoma cells, enabling identification of multiple tumor-associated antigens with therapeutic potential. Cellular trafficking assays and single-particle tracking reveal a global stabilization of HLA-I molecules, extension of their cell-surface lifetime and microdomain formation. HLA-Shuttle can be used across a range of aberrant cellular states where low antigen expression remains a bottleneck for the identification of endogenous peptide antigens.

Citations

• NetMHCpan-4.1 and NetMHCIIpan-4.0: improved predictions of MHC antigen presentation by concurrent motif deconvolution and integration of MS MHC eluted ligand data
• Cancer Immune Evasion Through Loss of MHC Class I Antigen Presentation
• IonQuant Enables Accurate and Sensitive Label-Free Quantification With FDR-Controlled Match-Between-Runs
• The present and future of the Cancer Dependency Map
• The Immune Epitope Database (IEDB): 2024 update
• The Genotype-Tissue Expression (GTEx) project

Discussions

• Researchers Nikolaos Sgourakis and John Maris from team NexTGen (co-funded by @themarkfdn.bsky.social) created a discovery system to identify new antigens in neuroblastoma. 📖 Read the Science Advanc [bsky, 1 points, 0 comments]

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