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Tumours recruit macrophages and immature myeloid cells and re-train them as bodyguards that switch off T cells, build vessels, and obey 'don't eat me' signals such as CD47.
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 landlord who hires the neighbourhood's own bouncers, pays them in sugar and lactate, and hangs a sign on every door that reads 'don't touch, friend' (CD47). The police (T cells) are stopped at the door by the bouncers, and the cleaners (macrophages) read the sign and leave.
A castle under siege from the inside: the cancer conscripts the town's builders (fibroblasts) to raise walls, bribes the guards (macrophages) to look away, and diverts the water supply (vessels) so that reinforcements (T cells, drugs) never arrive.
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.
Tumours recruit macrophages and immature myeloid cells and re-train them as bodyguards that switch off T cells, build vessels, and obey 'don't eat me' signals such as CD47.
Myeloid suppression: TAMs, MDSCs & don't-eat-me signals. Tumours recruit the body's clean-up cells (macrophages and immature myeloid cells) and re-train them as bodyguards. They switch off T cells, build vessels, and, when a therapeutic antibody flags a cancer cell for eating, are told 'don't eat me' by CD47 on its surface.
Tumour microenvironment (TME). A tumour is not just cancer cells. It is a neighbourhood of fibroblasts, immune cells, blood vessels, nerves, and scaffolding that the cancer recruits and corrupts, and that decides whether drugs and immune cells can get in.
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.
CD47 is the 'don't eat me' signal: it binds SIRP-alpha on macrophages to stop them engulfing the cell, and over 90% of AML blasts and large B-cell lymphoma cells display it. Blocking it should let macrophages eat tumour cells, but red cells carry CD47 too, so anaemia is built in, and the lead antibody magrolimab was dropped after failed trials.
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.
A chemokine receptor that anchors blood cells in the marrow and helps cancer cells home to it; mutated in a third of Waldenström patients and targeted by plerixafor for stem-cell mobilisation.
An immune checkpoint on myeloid cells that works at the acidic pH inside tumours and is a suspected escape route after PD-1 therapy; antibodies are in early trials.
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.
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.
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.
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.
MYC drives half of all cancers but has no pocket for a drug and is needed by normal cells too. The first direct MYC blockers are in trials; the question is whether there is a therapeutic window.
In immune-excluded tumours T cells reach the border but cannot get in, held back by fibroblasts, matrix, abnormal vessels, CXCL12 gradients or myeloid cells, and TGF-β drugs on their own have failed. If single-cell and spatial profiling can show which stromal programme dominates in each tumour, matching the drug (TGF-β, FAP, CXCR4 or VEGF) to it could let immunotherapy work.
Drugs that grab T cells and drag them onto tumours work well in blood cancers. The same trick aimed at tumour-eating cells might work where T cells are absent.
Some harmless bacteria naturally grow in the low-oxygen core of tumours. Engineering them to produce immune-activating drugs turns them into tiny factories inside the tumour.
Breathing in an immune-activating drug could turn the lungs into bad soil for cancer seeds, at doses far too low to cause body-wide side-effects.
Immunotherapy works in tumours that immune cells can enter and ignores those that shut them out. Systematically test ways to open up the shut-out tumours, measured with spatial maps.
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 6.4 of 56.