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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.
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.
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.
Shares Neoantigen, Antigen presentation & immune editing, The cancer-immunity cycle, Tumour mutational burden (TMB).
Shares Vinod P. Balachandran, Neoantigen, Nature, Tumour mutational burden (TMB).
Shares Vinod P. Balachandran, Neoantigen, Nature, Personalised neoantigen (mRNA) vaccines.
Shares Nature, Whole-exome & whole-genome sequencing, Memorial Sloan Kettering Cancer Center, Pancreatic ductal adenocarcinoma.
Shares Neoantigen, The cancer-immunity cycle, Tumour mutational burden (TMB), Whole-exome & whole-genome sequencing.
Shares Neoantigen, Antigen presentation & immune editing, Personalised neoantigen (mRNA) vaccines, Memorial Sloan Kettering Cancer Center.
Shares Immune exclusion, Nature.