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Three immune weathers: inflamed (T cells inside), excluded (stuck at the edge), desert (none). Most common cancers are cold. Radiation, viruses, STING agonists and vessel-opening drugs try to warm them; engagers and CAR-T bring their own T cells.
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.
Three kinds of town: one where the police already patrol the streets (inflamed), one where they mill about outside a wall (excluded), and one with no police station at all (desert). Removing the officers' handcuffs (PD-1 blockade) only helps in the first; the second needs a gate, the third needs recruitment.
A smoke detector wired to the fire brigade. DNA in the cytoplasm is smoke; cGAS is the detector; STING is the alarm bell; interferon is the 999 call that brings the immune system. Many tumours have quietly removed the batteries.
A town planner who first refuses all new building (tumour suppressor) and then, corrupted, builds walls and moats around the tumour that keep the police out (immune exclusion).
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.
Three immune weathers: inflamed (T cells inside), excluded (stuck at the edge), desert (none). Most common cancers are cold. Radiation, viruses, STING agonists and vessel-opening drugs try to warm them; engagers and CAR-T bring their own T cells.
Cold tumours: immune deserts and exclusion. Tumours come in three immune weathers: inflamed (T cells inside, checkpoint drugs work), excluded (T cells stuck at the edge), and desert (no T cells at all). Most common cancers are excluded or desert, and turning them 'hot' is the central problem of immunotherapy.
cGAS-STING innate sensing. cGAS-STING is the cell's alarm for DNA in the wrong place. Radiation, chemotherapy, and ADCs spill DNA into the cytoplasm; cGAS detects it, STING sounds the alarm, and interferon calls in the immune system.
TGF-β signalling. A signal that stops normal cells from dividing but, once a cancer is established, switches sides: it builds scar-like stroma, walls out immune cells, and pushes cells into a migratory state.
Wnt / β-catenin. Wnt/β-catenin is a developmental pathway hijacked by colorectal cancer. Normally a destruction complex keeps β-catenin low; losing APC lets it flood the nucleus and drive growth genes.
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.
The signal tumours use to grow their own blood supply. Blocking it starves tumours and, surprisingly, helps immunotherapy work.
EZH2 is an enzyme that silences genes. The first drug against it treated a rare sarcoma and some lymphomas until it was withdrawn in 2026 for causing second blood cancers.
FAP (fibroblast activation protein) sits on the cancer-associated fibroblasts that scaffold more than 90% of epithelial cancers and is almost absent from normal adult tissue. FAPI PET tracers therefore light up tumours with high contrast, including pancreatic, gastric and low-grade cancers where FDG PET is weak, and FAP-targeted radioligands are in development.
PD-1 is a brake on T cells. Blocking it releases the immune system against the tumour and has cured some previously incurable cancers.
PIK3CA is the most commonly mutated gene in hormone-driven breast cancer. Drugs against it work, but hitting it cleanly without raising blood sugar took years.
The receptor that macrophages depend on; blocking it shrinks tenosynovial giant cell tumour (a CSF1-driven tumour) and depletes tumour-supporting macrophages, though the latter has not yet helped patients with common cancers.
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.
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.
Pancreatic tumours are packed with a type of white blood cell that shuts down the immune attack. Blocking the signal that recruits them may open the tumour to immunotherapy.
Instead of finding a different target for each cancer, hit the scaffolding cells that almost all solid tumours share.
Rare cancers often share a broken cellular machine even when they arise in different organs. Grouping patients by that shared fault makes trials possible.
Most cancers have the wrong number of chromosomes; normal cells do not. If that difference creates a specific weakness, a drug against it would spare normal tissue by definition.
Ninety-five percent of bowel cancers ignore immunotherapy. Combinations that heat the tumour up (targeted drugs, radiation, new checkpoints) are the main hope.
Give immunotherapy before surgery rather than after, so the tumour is still present to teach the immune system, then look inside it to learn what happened.
Tumours fill with immune cells that protect them. Earlier drugs tried to remove those cells and failed. Newer ones aim to switch them to the attacking side.
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.
Injecting immune-activating agents into a single tumour, plus a small dose of radiation, can teach the immune system to attack tumours elsewhere in the body.
Whether immune cells are next to cancer cells matters more than how many there are. Turning that spatial picture into a reliable, standardised test would predict response better.
20 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 6.3 of 56.