{"entity":{"id":"paper-balachandran-neoantigen-quality-long-term-survivors-nature-2017","kind":"paper","name":"Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer","aka":[],"tldr":"The rare people who survive pancreatic cancer for years have tumours carrying both many mutation-made target proteins and plenty of killer T cells, and the quality of those targets, some resembling germ proteins, predicts long survival.","summary":"Genetic, immunohistochemical and transcriptional immunoprofiling, computational biophysics and functional assays were used to identify T-cell antigens in long-term survivors of pancreatic cancer. Whole-exome sequencing with in silico neoantigen prediction showed that tumours with both the highest neoantigen number and the most abundant CD8 T-cell infiltrates, but neither alone, stratified the longest survival. A neoantigen quality fitness model giving greater immunogenicity to neoantigens with differential presentation and homology to infectious disease peptides identified long-term survivors in two independent datasets, whereas a quantity model did not; MUC16 neoantigens featured. Intratumoural and lasting circulating T-cell reactivity to high-quality and MUC16 neoantigens was detected, and high-quality neoantigenic clones were selectively lost on metastatic progression, consistent with immunoediting.","asOf":"2026-09-24","links":[{"label":"Balachandran et al., Nature 2017: neoantigen quality in long-term survivors","url":"https://doi.org/10.1038/nature24462"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29132146/"}],"tags":[],"related":[],"cancers":["pancreatic"],"sections":[],"technologies":["neoantigen-mrna-vaccine","wes-wgs"],"targets":[],"drugs":[],"companies":[],"institutions":["mskcc"],"pathways":["antigen-presentation-immunoediting","cancer-immunity-cycle"],"terms":["neoantigen","tmb"],"trials":[],"people":["vinod-balachandran"],"bottlenecks":[],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2017,"doi":"10.1038/nature24462","pmid":"29132146","authors":"Balachandran VP, Luksza M, Zhao JN, et al.","paperType":"translational","findings":["Long-term survival required both high neoantigen number and abundant CD8 infiltrate.","A neoantigen quality model, including MUC16 neoantigens and microbial homology, predicted survival.","High-quality neoantigen clones were lost at metastasis."],"whatItMeans":"It is the proof that T cells can control pancreatic cancer in some people, and the scientific basis for the personalised neoantigen vaccines now in trials.","caveats":["Small long-term survivor cohorts.","The fitness model is computational and not a clinical test."],"changedPractice":false},"route":"/key-papers/paper-balachandran-neoantigen-quality-long-term-survivors-nature-2017/","neighbours":{"cancer":[{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"}],"technology":[{"id":"neoantigen-mrna-vaccine","kind":"technology","name":"Personalised neoantigen (mRNA) vaccines","route":"/technologies/neoantigen-mrna-vaccine/"},{"id":"wes-wgs","kind":"technology","name":"Whole-exome & whole-genome sequencing","route":"/technologies/wes-wgs/"}],"institution":[{"id":"mskcc","kind":"institution","name":"Memorial Sloan Kettering Cancer Center","route":"/institutions/mskcc/"}],"pathway":[{"id":"antigen-presentation-immunoediting","kind":"pathway","name":"Antigen presentation & immune editing","route":"/pathways/antigen-presentation-immunoediting/"},{"id":"cancer-immunity-cycle","kind":"pathway","name":"The cancer-immunity cycle","route":"/pathways/cancer-immunity-cycle/"}],"term":[{"id":"immune-exclusion","kind":"term","name":"Immune exclusion","route":"/terms/immune-exclusion/"},{"id":"neoantigen","kind":"term","name":"Neoantigen","route":"/terms/neoantigen/"},{"id":"tmb","kind":"term","name":"Tumour mutational burden (TMB)","route":"/terms/tmb/"}],"person":[{"id":"vinod-balachandran","kind":"person","name":"Vinod P. Balachandran","route":"/people/vinod-balachandran/"}],"journal":[{"id":"nature","kind":"journal","name":"Nature","route":"/journals/nature/"}]}}