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Sequencing 619 bowel cancers collected prospectively in two long-running health studies found four new recurrently mutated genes and showed that the tumours making the most abnormal proteins attract the most immune cells and their owners live longer, even among tumours with an intact DNA spell-checker.
Whole-exome sequencing of 619 incident colorectal cancers from prospective cohorts was integrated with tumour immunity, pathology and survival data. Recurrently mutated genes not previously appreciated in the disease were identified, including BCL9L, RBM10, CTCF and KLF5. Higher neoantigen load was positively associated with overall lymphocytic infiltration, tumour-infiltrating lymphocytes, memory T cells and colorectal-cancer-specific survival, and the association with tumour-infiltrating lymphocytes was evident even within microsatellite-stable tumours. Mutations in HLA genes and other components of the antigen-processing machinery were positively selected in lymphocyte-rich tumours.
Deposited as coadread_dfci_2016 on cBioPortal (619 exomes; MSI-high 91 of 529 assessable, CIMP-high 95 of 500).
It is the argument that immune biology matters across the whole disease rather than only in the mismatch repair deficient sixth, and the reason microsatellite-stable tumours with high neoantigen load are still being pursued for immunotherapy.
Shares Cell, Antigen presentation & immune editing, Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2), Neoantigen.
Shares B2M, Antigen presentation & immune editing, Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2), Neoantigen.
Shares Antigen presentation & immune editing, Neoantigen, The cancer-immunity cycle, Tumour mutational burden (TMB).
Shares Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2), Neoantigen, The cancer-immunity cycle, Tumour mutational burden (TMB).
Shares Broad Institute of MIT and Harvard, Dana-Farber Brigham Cancer Center, Whole-exome & whole-genome sequencing.
Shares Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2), Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR), BRAF, Colorectal cancer.
Shares Antigen presentation & immune editing, Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2), Neoantigen, Whole-exome & whole-genome sequencing.
Shares Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2), Neoantigen, The cancer-immunity cycle, Tumour mutational burden (TMB).