Journal article
Strong spontaneous tumor neoantigen responses induced by a natural human carcinogen
OncoImmunology, Vol.4(7), e1011492
2015
Abstract
A key to improving cancer immunotherapy will be the identification of tumor-specific “neoantigens” that arise from mutations and augment the resultant host immune response. In this study we identified single nucleotide variants (SNVs) by RNA sequencing of asbestos-induced murine mesothelioma cell lines AB1 and AB1-HA. Using the NetMHCpan 2.8 algorithm, the theoretical binding affinity of predicted peptides arising from high-confidence, exonic, non-synonymous SNVs was determined for the BALB/c strain. The immunoreactivity to 20 candidate mutation-carrying peptides of increased affinity and the corresponding wild-type peptides was determined using interferon-γ ELISPOT assays and lymphoid organs of non-manipulated tumor-bearing mice. A strong endogenous immune response was demonstrated to one of the candidate neoantigens, Uqcrc2; this response was detected in the draining lymph node and spleen. Antigen reactive cells were not detected in non-tumor bearing mice. The magnitude of the response to the Uqcrc2 neoantigen was similar to that of the strong influenza hemagglutinin antigen, a model tumor neoantigen. This work confirms that the approach of RNAseq plus peptide prediction and ELISPOT testing is sufficient to identify natural tumor neoantigens.
Details
- Title
- Strong spontaneous tumor neoantigen responses induced by a natural human carcinogen
- Authors/Creators
- J. Creaney (Author/Creator)S. Ma (Author/Creator)S.A. Sneddon (Author/Creator)M.R. Tourigny (Author/Creator)I.M. Dick (Author/Creator)J.S. Leon (Author/Creator)A. Khong (Author/Creator)S.A. Fisher (Author/Creator)R.A. Lake (Author/Creator)W.J. Lesterhuis (Author/Creator)A.K. Nowak (Author/Creator)S. Leary (Author/Creator)M.W. Watson (Author/Creator)B.W. Robinson (Author/Creator)
- Publication Details
- OncoImmunology, Vol.4(7), e1011492
- Publisher
- Taylor & Francis
- Identifiers
- 991005541144007891
- Copyright
- © 2015 The Author(s).
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases
- Language
- English
- Resource Type
- Journal article
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- Citation topics
- 1 Clinical & Life Sciences
- 1.6 Immunology
- 1.6.214 Checkpoint Inhibition
- Web Of Science research areas
- Immunology
- Oncology
- ESI research areas
- Biology & Biochemistry