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Strong spontaneous tumor neoantigen responses induced by a natural human carcinogen

Creaney, J., Ma, S., Sneddon, S.A., Tourigny, M.R., Dick, I.M., Leon, J.S., Khong, A., Fisher, S.A., Lake, R.A., Lesterhuis, W.J., Nowak, A.K., Leary, S., Watson, M.W.ORCID: 0000-0002-6438-9225 and Robinson, B.W. (2015) Strong spontaneous tumor neoantigen responses induced by a natural human carcinogen. OncoImmunology, 4 (7). e1011492.

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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.

Item Type: Journal Article
Murdoch Affiliation(s): Institute for Immunology and Infectious Diseases
Publisher: Taylor & Francis
Copyright: © 2015 The Author(s).
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