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The immune system removes abnormal cells all the time. Seven steps have to work: antigen released, picked up, T cells trained, dispatched, let in, target recognised, target killed. Tumours that exist are the ones that broke a step.
Pick a product above a diagram to see the nodes it hits and the escape routes below the block. Hover or tap any node or arrow for what it is; every node opens its target, glossary entry or the pathway page. Violet boxes are druggable targets.
A relay of seven runners. The race is only won if every baton is passed. Cancers usually drop only one or two batons, so the treatment that works is the one that fixes the step that actually failed, which is why the same drug cures one patient and does nothing for the next.
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).
Guards who stop anyone not wearing a staff badge (MHC-I) or anyone visibly panicking (stress ligands). Cancer's trick against T cells (throwing away the badge) makes it conspicuous to these guards, so successful tumours also learn to stop panicking, borrow a visitor badge (HLA-E) and bribe the guards with TGF-β.
In plain words, then the glossary entries the stage rests on. Chapter 1, The body's defences: Cancer is not the default.
The immune system removes abnormal cells all the time. Seven steps have to work: antigen released, picked up, T cells trained, dispatched, let in, target recognised, target killed. Tumours that exist are the ones that broke a step.
The cancer-immunity cycle. Seven steps the immune system must complete to kill a tumour: release of antigens, pick-up by dendritic cells, priming of T cells in lymph nodes, travel, entry into the tumour, recognition, and killing. Every immunotherapy pushes on one step; every escape blocks one.
Antigen presentation & immune editing. 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.
NK-cell recognition: missing self & stress ligands. Natural killer cells patrol for cells that have lost their identity papers (MHC-I) or that display stress flags. Cancers that hide from T cells by dropping MHC-I become visible to NK cells, unless they also shed the stress flags, wrap themselves in a second inhibitory badge (HLA-E), or soak the neighbourhood in TGF-β.
The proteins and genes at this stage, with their role and how many products act on each. Listed players come from the atlas; drawn players sit as nodes in the diagrams above.
PD-1 is a brake on T cells. Blocking it releases the immune system against the tumour and has cured some previously incurable cancers.
CD3 is the switch on every T cell. Bispecific drugs grab it with one arm and the tumour with the other, forcing the T cell to attack.
The first immune brake ever targeted for cancer; releasing it won a Nobel Prize and cures a fraction of melanomas.
A growth-signal receptor. Some cancers make far too much of it, and drugs that block it or use it as a docking site have transformed those cancers.
The signal tumours use to grow their own blood supply. Blocking it starves tumours and, surprisingly, helps immunotherapy work.
PD-L1 is the tumour's side of the PD-1 brake, and also the biomarker that decides who gets immunotherapy.
TIGIT is an inhibitory receptor on T and natural killer cells that binds PVR (CD155) on tumour cells, so blocking it was expected to amplify PD-1 and PD-L1 inhibitors. Tiragolumab, domvanalimab and others then failed to add benefit in phase 3 lung cancer trials despite encouraging phase 2 signals, and the lack of a TIGIT-specific biomarker remains a weakness.
Products grouped by the node they hit, most advanced first, with the cancers an approved product is linked to. Pick one above the diagram to see it light up.
Records tied to this stage that describe resistance, evasion or tolerance. Resistance: how tumours escape each drug class lists the routes class by class.
Two thirds of women treated on the KEYNOTE-522 regimen have no tumour left at surgery and about 92 percent of them are alive without relapse at five years, yet all receive nine more cycles of pembrolizumab. Trials are now testing whether the best responders can stop early, skip the anthracycline, or in lymphocyte-rich stage I tumours skip chemotherapy altogether.
Individualised mRNA cancer vaccines take weeks to manufacture and work best against minimal residual disease. Making the vaccine at surgery and giving it only when a blood tumour DNA test turns positive matches both facts and concentrates the cost on the minority who will relapse.
Personal cancer vaccines target a list of mutations, some present in only part of the tumour, so the tumour can escape by losing them. Restricting vaccines and T-cell products to clonal mutations shared by every tumour cell, identified by multi-region sequencing, should close that escape route.
Some tumours change fast and escape drugs quickly; others are stable. A single validated score for how evolvable a tumour is would tell doctors how aggressively to combine treatments.
Resistance often arrives as the same few mutations. Teaching the immune system to recognise them in advance could remove the escaping cells while they are still rare.
Biomarkers, tests and assays in the corpus that read this stage in a patient.
What is not known at this stage: the atlas's own questions, the bottlenecks it bears on, and the ideas in the corpus that try to answer them.
Several treatments now work without chemotherapy, but most are given until the disease comes back. Giving them for a fixed time and stopping is the version patients would choose.
Immunotherapy is often given for two years or until it stops working, but responses can last long after stopping. Trials that randomly assign responders to stop or continue would show whether the extra year is needed.
Small triple-negative tumours packed with immune cells almost never come back. The idea is to skip chemotherapy for those patients.
People with Lynch syndrome have a very high lifetime cancer risk from a predictable set of mutations. Vaccinate them against those shared mutations before cancer appears.
Lynch syndrome tumours share predictable mutations the immune system can target. A vaccine in early trials could be tested to see if it prevents polyps and cancers in carriers.
Tumour mutational burden decides who gets immunotherapy in some settings, but every sequencing panel calculates it differently. A shared calibration would make the number mean the same thing everywhere.
Stomach cancer now has three add-on biomarkers (HER2, PD-L1, Claudin 18.2) that often overlap. Test whether combining two add-ons beats picking one.
Add immunotherapy to the two targeted pills in the most aggressive thyroid cancer, because the combination has produced multi-year survivors in early series.
Scan for T cells inside the tumour a few weeks after starting immunotherapy. If they have not arrived, change course.
A single-centre trial at Tata Memorial found that adding nivolumab at about a twentieth of the usual dose to chemotherapy improved outcomes in head and neck cancer. Confirmatory trials against standard-dose immunotherapy are needed before low-dose labels could make immunotherapy affordable for millions.
26 more ideas are linked to this stage's pathways, targets and terms; see the rankings →
Papers in the corpus tied to this stage's pathways, targets and terms, newest first.
src/data/mechanics-atlas.ts). Players, medicines, escape routes, tests, ideas and papers are resolved from the knowledge graph at build time through the stage's pathways, targets and terms, so every item here has its own page and sources. Where a section is missing, the corpus has no record tied to the stage yet. Nothing here is medical advice; see about and methodology. Stage 1.2 of 56.