Mass Spectrometry-Based Profiling of Personalized Immunopeptidomes in Thai Renal Cell Carcinoma
peer-reviewed · Journal of Proteome Research · 2026
| Date | 2026-09-04 |
| Type | peer-reviewed |
| Venue | Journal of Proteome Research |
| Publisher | American Chemical Society (ACS) |
| Contribution | downstream-application |
| DOI | 10.1021/acs.jproteome.6c00141 |
| Citations (OpenAlex) | 0 |
| Venue 2-year citedness | 3.83 |
Abstract
This study profiles the personalized immunopeptidomes of 13 Thai patients with renal cell carcinoma (RCC), addressing a critical knowledge gap in Southeast Asian populations characterized by distinct HLA allele distributions. We combined whole-exome sequencing (WES)-based personalized proteome construction with liquid chromatography-tandem mass spectrometry (LC-MS/MS), using both database-driven searches and de novo peptide sequencing. HLA typing identified several class I allotypes that are underrepresented in publicly available immunopeptidome resources, including seven alleles not previously represented in the databases examined; HLA-A*11:01 was the most frequent allele in this cohort. Database-based analysis identified a single tumor-specific neoantigen derived from a mutant JADE2 peptide in the patient with the highest tumor mutational burden, which was validated by a mutant-specific ELISPOT response. In contrast, de novo sequencing revealed numerous noncanonical peptides, a subset of which were supported by proteogenomic validation using PepQuery and detected exclusively in cancer proteomes but not in normal tissue data sets, indicating their potential as tumor-associated antigen candidates. Together, these results establish an integrated and scalable framework for identifying HLA-presented tumor-derived peptides and provide a foundational immunopeptidome resource to support personalized cancer immunotherapy development in Southeast Asia.
Methods and tools
- Thai RCC personalised immunopeptidomics: Profiles the personalised immunopeptidomes of 13 Thai renal cell carcinoma patients, whose HLA allotypes are underrepresented in public reference data. Builds a personalised proteome from whole-exome sequencing and searches it alongside de novo peptide sequencing, so de novo produced part of the result.
Data used
Cites (5)
- MARS an improved de novo peptide candidate selection method for non-canonical antigen target discovery in cancer (2024) crossref
- Unsupervised Mining of HLA-I Peptidomes Reveals New Binding Motifs and Potential False Positives in the Community Database (2022) crossref
- Digging deeper into the immunopeptidome: characterization of post-translationally modified peptides presented by MHC I (2021) crossref
- Proteogenomics and de novo sequencing based approach for neoantigen discovery from the immunopeptidomes of patient CRC liver metastases using Mass Spectrometry (2020) crossref
- Uncovering Thousands of New Peptides with Sequence-Mask-Search Hybrid De Novo Peptide Sequencing Framework (2019) crossref