{"entity":{"id":"antigen-presentation-immunoediting","kind":"pathway","name":"Antigen presentation & immune editing","aka":[],"tldr":"How the immune system sees cancer, and how cancer learns to hide. Tumours display fragments of their proteins on MHC molecules; T cells kill the ones they recognise; the survivors are the ones that stopped showing fragments or switched on brakes.","summary":"Proteasome-processed peptides are loaded on MHC class I (HLA-A/B/C, B2M) and presented to CD8 T cells; dendritic cells cross-present tumour antigens in lymph nodes. Immunoediting proceeds through elimination, equilibrium, and escape: loss of B2M or HLA, JAK1/2 or IFNGR mutations (blunting interferon-γ response), antigen loss, PD-L1 induction, and immunosuppressive niches. Neoantigen quality, not just quantity, predicts response; HLA genotype shapes which mutations are visible. Escape variants explain acquired resistance to checkpoint blockade and CAR-T (CD19 loss).","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Immunoediting","links":[{"label":"Schreiber, Old & Smyth, Cancer immunoediting (Science 2011)","url":"https://doi.org/10.1126/science.1203486"},{"label":"Zaretsky et al., Mutations associated with acquired resistance to PD-1 blockade (NEJM 2016)","url":"https://doi.org/10.1056/NEJMoa1604958"}],"tags":["mechanism"],"related":[],"cancers":["tnbc","non-hodgkin-lymphoma"],"sections":[],"technologies":["neoantigen-mrna-vaccine","tcr-t","t-cell-engager","car-t","car-nk-macrophage","checkpoint-inhibitor"],"targets":["pd1","pdl1","cd3","gp100","mage-a4","prame","hla-a"],"drugs":[],"companies":[],"institutions":["wustl-siteman","mskcc","nci","johns-hopkins"],"pathways":["pd1-checkpoint","cgas-sting","jak-stat"],"terms":["neoantigen","hla-a02-restriction","tmb","cold-vs-hot","avoiding-immune-destruction"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-zaretsky-n-engl-j-med"],"journals":[],"dependsOn":[],"notes":["Leading programmes: Schreiber (WashU) coined immunoediting; Chan and Ribas on neoantigen quality and escape (MSK, UCLA); NCI Surgery Branch on neoantigen-reactive T cells; Balachandran (MSK) on long-term vaccine responders."],"analogy":"Wanted posters: the cell pins fragments of everything it makes onto its surface. Immune police recognise criminals' faces. Cancers that survive have taken down the posters (lost MHC) or bribed the police (checkpoints).","nodes":[{"id":"prot","label":"Proteasome → peptides","x":15,"y":30},{"id":"tap","label":"TAP transport","x":35,"y":30},{"id":"mhc","label":"MHC-I / B2M loading","x":55,"y":30},{"id":"surf","label":"Peptide-MHC on surface","x":75,"y":30},{"id":"tcr","label":"CD8 T cell (TCR)","x":75,"y":65,"targetId":"cd3"},{"id":"ifn","label":"IFN-γ → JAK1/2 → STAT1","x":45,"y":65},{"id":"pdl1","label":"PD-L1 induction","x":25,"y":85,"targetId":"pdl1"},{"id":"dc","label":"Dendritic cell cross-presentation","x":92,"y":50},{"id":"escape","label":"Escape: B2M/HLA loss, JAK mutation","x":15,"y":60}],"edges":[{"from":"prot","to":"tap","type":"activates"},{"from":"tap","to":"mhc","type":"activates"},{"from":"mhc","to":"surf","type":"activates"},{"from":"surf","to":"tcr","type":"activates"},{"from":"dc","to":"tcr","type":"activates"},{"from":"tcr","to":"ifn","type":"activates"},{"from":"ifn","to":"mhc","type":"activates"},{"from":"ifn","to":"pdl1","type":"activates"},{"from":"pdl1","to":"tcr","type":"inhibits"},{"from":"escape","to":"mhc","type":"inhibits"},{"from":"escape","to":"ifn","type":"inhibits"}],"interventions":["Checkpoint inhibitors; personalised neoantigen vaccines (intismeran) supply antigen; T-cell engagers and CAR-T bypass MHC entirely","TCR-T and ImmTACs (tebentafusp) target intracellular antigens via peptide-HLA","Epigenetic drugs and interferon can re-express MHC; MHC-independent NK-cell therapies address MHC-loss escape"]},"route":"/pathways/antigen-presentation-immunoediting/","neighbours":{"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"hiv-associated-lymphoma","kind":"cancer","name":"HIV-associated (AIDS-related) lymphomas","route":"/cancers/hiv-associated-lymphoma/"},{"id":"hodgkin-lymphoma","kind":"cancer","name":"Hodgkin lymphoma","route":"/cancers/hodgkin-lymphoma/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"},{"id":"post-transplant-lymphoproliferative-disorder","kind":"cancer","name":"Post-transplant lymphoproliferative disorder (PTLD)","route":"/cancers/post-transplant-lymphoproliferative-disorder/"},{"id":"primary-cns-lymphoma","kind":"cancer","name":"Primary CNS lymphoma","route":"/cancers/primary-cns-lymphoma/"},{"id":"primary-mediastinal-b-cell-lymphoma","kind":"cancer","name":"Primary mediastinal (thymic) large B-cell lymphoma","route":"/cancers/primary-mediastinal-b-cell-lymphoma/"},{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"}],"technology":[{"id":"car-nk-macrophage","kind":"technology","name":"CAR-NK & CAR-macrophage","route":"/technologies/car-nk-macrophage/"},{"id":"car-t","kind":"technology","name":"CAR-T cell therapy","route":"/technologies/car-t/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"},{"id":"neoantigen-mrna-vaccine","kind":"technology","name":"Personalised neoantigen (mRNA) vaccines","route":"/technologies/neoantigen-mrna-vaccine/"},{"id":"t-cell-engager","kind":"technology","name":"T-cell engagers (bispecific)","route":"/technologies/t-cell-engager/"},{"id":"tcr-t","kind":"technology","name":"TCR-T cell therapy","route":"/technologies/tcr-t/"}],"target":[{"id":"b2m","kind":"target","name":"B2M","route":"/targets/b2m/"},{"id":"cd3","kind":"target","name":"CD3","route":"/targets/cd3/"},{"id":"cd30","kind":"target","name":"CD30","route":"/targets/cd30/"},{"id":"ciita","kind":"target","name":"CIITA","route":"/targets/ciita/"},{"id":"gp100","kind":"target","name":"gp100 (PMEL)","route":"/targets/gp100/"},{"id":"hla-a","kind":"target","name":"HLA-A","route":"/targets/hla-a/"},{"id":"jak1","kind":"target","name":"JAK1","route":"/targets/jak1/"},{"id":"jak2","kind":"target","name":"JAK2","route":"/targets/jak2/"},{"id":"mage-a4","kind":"target","name":"MAGE-A4","route":"/targets/mage-a4/"},{"id":"pd1","kind":"target","name":"PD-1","route":"/targets/pd1/"},{"id":"pdl1","kind":"target","name":"PD-L1","route":"/targets/pdl1/"},{"id":"prame","kind":"target","name":"PRAME","route":"/targets/prame/"},{"id":"stat1","kind":"target","name":"STAT1","route":"/targets/stat1/"}],"institution":[{"id":"johns-hopkins","kind":"institution","name":"Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer Center","route":"/institutions/johns-hopkins/"},{"id":"mskcc","kind":"institution","name":"Memorial Sloan Kettering Cancer Center","route":"/institutions/mskcc/"},{"id":"nci","kind":"institution","name":"National Cancer Institute (NIH)","route":"/institutions/nci/"},{"id":"wustl-siteman","kind":"institution","name":"Siteman Cancer Center, Washington University","route":"/institutions/wustl-siteman/"}],"pathway":[{"id":"autophagy","kind":"pathway","name":"Autophagy","route":"/pathways/autophagy/"},{"id":"cd47-sirpa","kind":"pathway","name":"CD47 / SIRPα (the 'don't eat me' signal)","route":"/pathways/cd47-sirpa/"},{"id":"cgas-sting","kind":"pathway","name":"cGAS-STING innate sensing","route":"/pathways/cgas-sting/"},{"id":"jak-stat","kind":"pathway","name":"JAK-STAT signalling","route":"/pathways/jak-stat/"},{"id":"mismatch-repair-msi","kind":"pathway","name":"Mismatch repair & microsatellite instability","route":"/pathways/mismatch-repair-msi/"},{"id":"nk-cell-recognition","kind":"pathway","name":"NK-cell recognition: missing self & stress ligands","route":"/pathways/nk-cell-recognition/"},{"id":"oncogenic-viruses","kind":"pathway","name":"Oncogenic viruses","route":"/pathways/oncogenic-viruses/"},{"id":"pd1-checkpoint","kind":"pathway","name":"PD-1 / PD-L1 immune checkpoint & T-cell activation","route":"/pathways/pd1-checkpoint/"},{"id":"resistance-routes-map","kind":"pathway","name":"Resistance routes: how a blocked pathway comes back","route":"/pathways/resistance-routes-map/"},{"id":"rna-splicing","kind":"pathway","name":"RNA splicing","route":"/pathways/rna-splicing/"},{"id":"t-cell-exhaustion","kind":"pathway","name":"T-cell exhaustion","route":"/pathways/t-cell-exhaustion/"},{"id":"cancer-immunity-cycle","kind":"pathway","name":"The cancer-immunity cycle","route":"/pathways/cancer-immunity-cycle/"}],"term":[{"id":"antigen","kind":"term","name":"Antigen","route":"/terms/antigen/"},{"id":"avoiding-immune-destruction","kind":"term","name":"Hallmark: avoiding immune destruction","route":"/terms/avoiding-immune-destruction/"},{"id":"hla-a02-restriction","kind":"term","name":"HLA-A*02:01 restriction","route":"/terms/hla-a02-restriction/"},{"id":"cold-vs-hot","kind":"term","name":"Hot vs cold tumours","route":"/terms/cold-vs-hot/"},{"id":"immune-surveillance-immunoediting","kind":"term","name":"Immune surveillance and cancer immunoediting","route":"/terms/immune-surveillance-immunoediting/"},{"id":"neoantigen","kind":"term","name":"Neoantigen","route":"/terms/neoantigen/"},{"id":"lymphoma-bio-hodgkin-microenvironment","kind":"term","name":"The Hodgkin microenvironment: when the cancer cell is the minority","route":"/terms/lymphoma-bio-hodgkin-microenvironment/"},{"id":"tmb","kind":"term","name":"Tumour mutational burden (TMB)","route":"/terms/tmb/"}],"paper":[{"id":"paper-connor-mutational-signatures-immune-pancreatic-jama-oncol-2017","kind":"paper","name":"Association of distinct mutational signatures with correlates of increased immune activity in pancreatic ductal 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instability","route":"/key-papers/paper-mlecnik-immunoscore-msi-colorectal-immunity-2016/"},{"id":"paper-iwai-pdl1-tumour-escape-pnas-2002","kind":"paper","name":"Iwai and Honjo: tumours use PD-L1 to escape T cells, and blocking it restores attack","route":"/key-papers/paper-iwai-pdl1-tumour-escape-pnas-2002/"},{"id":"paper-lehmann-tnbc-subtype-multiomics-nat-commun-2021","kind":"paper","name":"Multi-omics analysis identifies therapeutic vulnerabilities in triple-negative breast cancer subtypes","route":"/key-papers/paper-lehmann-tnbc-subtype-multiomics-nat-commun-2021/"},{"id":"paper-zaretsky-n-engl-j-med","kind":"paper","name":"Mutations Associated with Acquired Resistance to PD-1 Blockade in Melanoma","route":"/key-papers/paper-zaretsky-n-engl-j-med/"},{"id":"paper-bareche-tnbc-microenvironment-jnci-2020","kind":"paper","name":"Unraveling triple-negative breast cancer tumor microenvironment heterogeneity: towards an optimized treatment approach","route":"/key-papers/paper-bareche-tnbc-microenvironment-jnci-2020/"}],"biomarker":[{"id":"pd-ligand-9p24-alteration","kind":"biomarker","name":"9p24.1 alteration of the PD-1 ligand loci","route":"/biomarkers/pd-ligand-9p24-alteration/"}],"idea":[{"id":"idea-splice-neoantigens","kind":"idea","name":"Shared splice-derived neoantigens as off-the-shelf vaccine targets","route":"/ideas/idea-splice-neoantigens/"},{"id":"idea-neoantigen-immunogenicity-rules","kind":"idea","name":"What makes a neoantigen actually immunogenic?","route":"/ideas/idea-neoantigen-immunogenicity-rules/"}]}}