{"entity":{"id":"paper-giannakis-genomic-correlates-immune-colorectal-cell-rep-2016","kind":"paper","name":"Genomic correlates of immune-cell infiltrates in colorectal carcinoma","aka":[],"tldr":"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.","summary":"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.\n\nDeposited as coadread_dfci_2016 on cBioPortal (619 exomes; MSI-high 91 of 529 assessable, CIMP-high 95 of 500).","asOf":"2026-09-24","links":[{"label":"Giannakis et al., Cell Reports 2016: exomes of 619 incident colorectal cancers with immune, pathology and survival data","url":"https://doi.org/10.1016/j.celrep.2016.03.075"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/27149842/"},{"label":"cBioPortal study coadread_dfci_2016 (DFCI, Cell Reports 2016; 619 exomes from the Nurses' Health Study and Health Professionals Follow-up Study, no copy-number profile)","url":"https://www.cbioportal.org/study/summary?id=coadread_dfci_2016"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":["wes-wgs"],"targets":["b2m","braf","mmr"],"drugs":[],"companies":[],"institutions":["dana-farber","broad-institute"],"pathways":["cancer-immunity-cycle","antigen-presentation-immunoediting"],"terms":["neoantigen","msi","tmb"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cell"],"dependsOn":[],"notes":[],"journal":"Cell Reports","year":2016,"doi":"10.1016/j.celrep.2016.03.075","pmid":"27149842","authors":"Giannakis M, Mu XJ, Shukla SA, et al.","paperType":"observational","findings":["New recurrently mutated genes: BCL9L (46 of 619), RBM10, CTCF, KLF5.","Neoantigen load associated with lymphocytic infiltration and cancer-specific survival, including within microsatellite-stable tumours.","Positive selection on HLA and antigen-processing genes in lymphocyte-rich tumours."],"whatItMeans":"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.","caveats":["Prospective cohorts of health professionals; not a random population sample.","Neoantigen prediction depends on the algorithm.","Exome only, so fusions and copy number are not covered."],"changedPractice":false,"participants":619},"route":"/key-papers/paper-giannakis-genomic-correlates-immune-colorectal-cell-rep-2016/","neighbours":{"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"}],"technology":[{"id":"wes-wgs","kind":"technology","name":"Whole-exome & whole-genome sequencing","route":"/technologies/wes-wgs/"}],"target":[{"id":"b2m","kind":"target","name":"B2M","route":"/targets/b2m/"},{"id":"braf","kind":"target","name":"BRAF","route":"/targets/braf/"},{"id":"mmr","kind":"target","name":"Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2)","route":"/targets/mmr/"}],"institution":[{"id":"broad-institute","kind":"institution","name":"Broad Institute of MIT and Harvard","route":"/institutions/broad-institute/"},{"id":"dana-farber","kind":"institution","name":"Dana-Farber Brigham Cancer Center","route":"/institutions/dana-farber/"}],"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":"msi","kind":"term","name":"Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR)","route":"/terms/msi/"},{"id":"neoantigen","kind":"term","name":"Neoantigen","route":"/terms/neoantigen/"},{"id":"tmb","kind":"term","name":"Tumour mutational burden (TMB)","route":"/terms/tmb/"}],"journal":[{"id":"cell","kind":"journal","name":"Cell","route":"/journals/cell/"}]}}