Predicting immunogenic tumour mutations by combining mass spectrometry and exome sequencing

  title={Predicting immunogenic tumour mutations by combining mass spectrometry and exome sequencing},
  author={Mahesh Yadav and Suchit Jhunjhunwala and Qui T. Phung and Patrick J. Lupardus and Josh Tanguay and Stephanie M Bumbaca and Christian Franci and Tommy K. Cheung and Jens Fritsche and Toni Weinschenk and Zora Modru{\vs}an and Ira Mellman and Jennie R. Lill and L{\'e}lia Delamarre},
Human tumours typically harbour a remarkable number of somatic mutations. If presented on major histocompatibility complex class I molecules (MHCI), peptides containing these mutations could potentially be immunogenic as they should be recognized as ‘non-self’ neo-antigens by the adaptive immune system. Recent work has confirmed that mutant peptides can serve as T-cell epitopes. However, few mutant epitopes have been described because their discovery required the laborious screening of patient… 


The techniques for cancer vaccine candidate selection and formulation, vaccine delivery systems, and the potential for use in combination with other therapeutics are discussed, with it anticipated that MS-based techniques will play an important role in future cancer vaccine development.

Direct identification of clinically relevant neoepitopes presented on native human melanoma tissue by mass spectrometry

It is concluded that direct identification of mutated peptide ligands from primary tumour material by MS is possible and yields true neoepitopes with high relevance for immunotherapeutic strategies in cancer.

Antigen Presentation Profiling Reveals Recognition of Lymphoma Immunoglobulin Neoantigens

This work discovers neoantigens in human mantle-cell lymphomas by using an integrated genomic and proteomic strategy that interrogates tumour antigen peptides presented by major histocompatibility complex (MHC) class I and class II molecules.

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Exome Sequencing to Predict Neoantigens in Melanoma

A high-throughput screening approach was used to identify mutated proteins processed and displayed by patient tumors and recognized by circulating immune cells, leading to seven mutated antigens in total that stimulated T-effector memory cells in two patients.



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The MHC class I peptide repertoire is molded by the transcriptome

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Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer

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The data suggest that holes in the functional T cell repertoire, if they exist, may be relatively rare and correlate well with class I binding affinity measurements of either naturally processed peptides or previously described T cell epitopes.