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Cells pin fragments of their proteins on MHC molecules like wanted posters. T cells read them. Tumours take the posters down (MHC or B2M loss) or lose the mutant proteins that made them visible. Engagers and CAR-T bypass the posters entirely.
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.
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).
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.
In plain words, then the glossary entries the stage rests on. Chapter 6, Escaping the immune system: Every tumour that exists has already beaten the immune system once.
Cells pin fragments of their proteins on MHC molecules like wanted posters. T cells read them. Tumours take the posters down (MHC or B2M loss) or lose the mutant proteins that made them visible. Engagers and CAR-T bypass the posters entirely.
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.
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.
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.
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.
PRAME is a cancer-testis antigen: a protein normally confined to the testis that about 90% of cutaneous melanomas and substantial fractions of ovarian, lung, endometrial and uveal cancers switch on. Because it sits inside the cell, drugs reach it only as peptide fragments displayed on HLA, through T-cell receptor bispecifics such as brenetafusp and TCR-T cells such as IMA203.
gp100 is a pigment-cell protein, and the target of the first bispecific drug to improve survival in a solid tumour, uveal melanoma.
A protein normally only in testis that some sarcomas and other tumours switch on; T cells can be engineered to recognise fragments of it.
PD-1 is a brake on T cells. Blocking it releases the immune system against the tumour and has cured some previously incurable 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.
The first immune brake ever targeted for cancer; releasing it won a Nobel Prize and cures a fraction of melanomas.
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.
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.
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.
Vaccines tailored to each patient's tumour mutations are showing real benefit but cost a fortune to make. Automate the whole process so a personalised vaccine costs about as much as a course of chemotherapy.
Ninety-five percent of advanced bowel cancers ignore immunotherapy, and the only real signal so far came in patients without active liver secondaries. Trials keep enrolling by treatment line rather than by immune biology, which guarantees the responders are diluted away.
Cells chop up their internal proteins and display the pieces on their surface. That means even undruggable proteins inside the cell can be attacked from outside by the immune system.
Some tumours have broken the machinery that displays their identity to immune cells. Those patients cannot benefit from most immunotherapy and should be routed elsewhere.
Today's engineered T-cell therapies for sarcoma only work in the ~40-50% of people with one particular HLA type; new receptors for other HLA types would open them to everyone.
Today's T-cell-receptor drugs only work for people with one tissue type. Building versions for the other common types would roughly double who can be treated.
3 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 6.1 of 56.