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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.
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).
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).
It gives the PD-L1-negative mesenchymal subtype, the group immunotherapy leaves behind, a mechanistic route back to immune visibility, and explains why immune infiltration and subtype are coupled.
One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.
It links the Lehmann subtypes to the spatial immune classes of Gruosso and gives a rationale for pairing checkpoint inhibitors with the immunomodulatory subtype and stromal or metabolic agents with the cold ones.
Fibroblasts are part of the immune conversation, not just a physical barrier, which is why stromal and immune strategies are now designed together.
It gives a genetic account of both immunotherapy failures: why some mismatch repair deficient tumours resist, and why the microsatellite-stable majority has no T cells in it to begin with.
Signatures find repair-deficient tumours that gene panels miss, and they mark the minority in which checkpoint drugs have a rationale.
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.
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 Unraveling triple-negative breast cancer tumor microenvironment heterogeneity: towards an optimized treatment approach, CD47 / SIRPα (the 'don't eat me' signal), Cross-species single-cell analysis of pancreatic ductal adenocarcinoma reveals antigen-presenting cancer-associated fibroblasts, Integrative analyses of colorectal cancer show Immunoscore is a stronger predictor of patient survival than microsatellite instability and the tag mechanism.
Shares Hallmark: avoiding immune destruction, NK-cell recognition: missing self & stress ligands, Hot vs cold tumours, PD-1 / PD-L1 immune checkpoint & T-cell activation and the tag mechanism.
Shares Multi-omics analysis identifies therapeutic vulnerabilities in triple-negative breast cancer subtypes, B2M, T-cell exhaustion, Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer Center and the tag mechanism.
Shares cGAS-STING innate sensing, Comprehensive genomic characterization of squamous cell lung cancers, Memorial Sloan Kettering Cancer Center, Pancreatic ductal adenocarcinoma and the tag mechanism.
Shares CD30, JAK-STAT signalling, Oncogenic viruses, Primary CNS lymphoma and the tag mechanism.
Shares Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer Center, PD-1 / PD-L1 immune checkpoint & T-cell activation, PD-1, Pancreatic ductal adenocarcinoma and the tag mechanism.
Shares RNA splicing, HIV-associated (AIDS-related) lymphomas, Non-Hodgkin lymphoma (all types), Triple-negative breast cancer (TNBC) and the tag mechanism.
Shares PD-1 / PD-L1 immune checkpoint & T-cell activation, Memorial Sloan Kettering Cancer Center, Immune checkpoint inhibitors and the tag mechanism.