Somatic mutations and gene losses in HLA class I genes—which cancer vaccines depend on—were found in over half of analyzed tumors, potentially explaining why personalized neoantigen vaccines work in some patients but not others.
>50%Of 24 cancer patients analyzed, more than half had some form of HLA class I gene disruption in their tumors that could impair personalized vaccine effectiveness
What the researchers found
Among 24 cancer patients, somatic HLA class I gene mutations were found in 5 patients, HLA gene loss of heterozygosity in 5 patients, and chromosome 6 copy loss in 8 patients—indicating over half had some form of HLA gene disruption that could undermine personalized neoantigen vaccine therapy.
Why it matters
Personalized cancer vaccines are a cutting-edge treatment with enormous promise, but variable response rates. If HLA gene disruption is common in tumors and routinely overlooked, it explains why some patients fail to respond—and points to a simple diagnostic step that could improve patient selection.
The numbers in context
- 24 patients analyzed with paired tumor-normal sequencing
- 5 patients (20.8%) had somatic HLA mutations in tumor
- 5 patients (20.8%) had HLA loss of heterozygosity
- 8 patients (33.3%) had chromosome 6 copy loss
How the study worked
Cross-sectional integrative genomic analysis using whole-exome sequencing (paired tumor-normal) and RNAseq from 24 cancer patients; four HLA typing tools used; somatic mutations, loss of heterozygosity, and chromosome copy number analyzed.
Who was studied
N=24 cancer patients with paired tumor-normal whole-exome sequencing and tumor RNA sequencing data.
What this study cannot tell us
Very small sample size (n=24) limits generalizability. Cross-sectional design cannot determine causality. Only HLA class I was assessed—HLA class II disruption was not analyzed. Different cancer types were pooled together.
How to read the evidence
Rated preliminary: very small sample (n=24), cross-sectional design, pooled cancer types, and no clinical outcomes data linking HLA disruption to actual vaccine failure.
When this study was published
Published in 2025 in JCO Clinical Cancer Informatics.
The bigger picture
This work addresses a critical gap in the personalized cancer vaccine field. As neoantigen vaccines enter clinical trials and early commercial development, understanding why they fail in some patients is essential for refining patient selection and improving response rates.
Questions still open
- Should HLA gene integrity screening become standard before personalized cancer vaccine therapy?
- Can tumors with partial HLA disruption still respond to vaccine therapy?
- How do HLA-disrupted tumors escape immune surveillance through other mechanisms?
Common questions
What are HLA genes and why do they matter for cancer vaccines?
Can patients with HLA gene disruptions still benefit from cancer immunotherapy?
Read the original research
Assessment of Functional Status of Human Leukocyte Antigen Class I Genes in Cancer Tissues in the Context of Personalized Neoantigen Peptide Vaccine Immunotherapy.
JCO clinical cancer informatics, 9, e2400174
Citation
Padul, Vijay G; Biswas, Nupur; Gill, Mini; Perez, Jesus A; Lopez, Javier J; Kesari, Santosh; Ashili, Shashanka. (2025). Assessment of Functional Status of Human Leukocyte Antigen Class I Genes in Cancer Tissues in the Context of Personalized Neoantigen Peptide Vaccine Immunotherapy.. JCO clinical cancer informatics, 9, e2400174. https://doi.org/10.1200/CCI-24-00174