✦ Overview
The identification of (neo)antigens is of paramount importance for the development of effective cancer immunotherapies. Neoantigens, derived from tumor-specific mutations, can be recognized by the immune system and serve as critical targets for personalized cancer treatments. Accurate identification and characterization of these neoantigens can significantly enhance the efficacy of immunotherapies, such as checkpoint inhibitors, adoptive T cell therapies, and personalized cancer vaccines, by improving their ability to target cancer cells while sparing healthy tissues. MS-based immunopeptidomics, the large-scale study of peptides presented by MHC molecules, has become an essential field for understanding tumor immunology. For instance, adoptive T cell therapies, such as T cell receptor (TCR) transgenic T cells and chimeric antigen receptor (CAR) T cells, rely on the precise identification of tumor-specific peptides to enhance their targeting capabilities and efficacy. Moreover, understanding the immunopeptidome can aid in the prediction of patient responses to checkpoint inhibitors, thereby optimizing treatment strategies. More than a dozen mutation-derived neoantigens have been reported from immunopeptidomic analysis of cancer cell lines and tumor samples.
The Ligand.MHC Atlas provides a comprehensive and tumor-specific atlas of MHC-bound peptides identified in various human cancers. As to July 2024, our database contained 305.7 million tandem mass spectra obtained from 112 published MS-based immunopeptidomic datasets. By re-analyzing the whole raw files using a high-performance search engine (pFind software), it yielded 24,380,595 and 7,300,227 peptide-spectrum matches (PSMs) for MHC class I immunopeptidome and class II immunopeptidome, respectively. Peptides were deconvolved and annotated to specific MHC alleles. In total, we identified 642,324 MHC-I bound peptides and 375,672 MHC-II bound peptides covering 292 HLA alleles across 26 cancer types (54 subtypes), greatly expanding the cancer immunopeptidome. Overall, through a more extensive and detailed collection of tumor-derived immunopeptidome data, our database provides a comprehensive and tumor-specific atlas of HLA-bound peptides identified in various human cancers. The Ligand.MHC Atlas can serve as a valuable resource to provide key insights into immunology and proteomics studies, and will accelerate the development of vaccines and immunotherapies against various immune-related diseases.
✦ Example
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✦ Developers:
Zhi Ran, Meilin Mu, Shaofeng Lin, Shengbao Suo, Kai Yuan, Haodong Xu @ CIMB, Central South University.