Nutrient competition
Tumour and immune cells eat from the same plate. Cancer hoards glucose, dumps lactate and acid, and burns tryptophan and arginine into by-products that paralyse T cells. Fixing the food fight is part of making immunotherapy work.
Diagram
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 buffet where the tumour arrives first, eats the protein, and leaves the table sticky with lactate. The immune guests arrive hungry and find nothing but by-products that make them drowsy.
What happens
In plain words, then the glossary entries the stage rests on. Chapter 5, Feeding the tumour: A tumour is a construction site that never stops.
Tumour and immune cells eat from the same plate. Cancer hoards glucose, dumps lactate and acid, and burns tryptophan and arginine into by-products that paralyse T cells. Fixing the food fight is part of making immunotherapy work.
Nutrient competition & metabolic immunosuppression. Tumours and immune cells eat from the same plate. Cancer cells hoard glucose and glutamine, dump lactate and acid, and burn tryptophan and arginine into by-products that paralyse T cells. The tumour wins the food fight, and the immune system loses before it has fired a shot.
The molecular players
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.
CD73 is an enzyme on tumour and immune cells that converts AMP into adenosine, which switches off T and natural killer cells through A2A and A2B receptors. Oleclumab (anti-CD73) with durvalumab slowed progression in a phase 2 lung cancer trial and quemliclustat is in phase 3 in pancreatic cancer, but A2A blockers gave only modest signals and several were dropped.
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 master switch that kidney cancer cells leave permanently on when they lose the VHL gene; belzutifan blocks it.
Where medicines act
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.
- CadonilimabApprovedCervical cancerGastric & gastro-oesophageal junction cancer
- CamrelizumabApprovedOesophageal cancerHepatocellular carcinomaNon-small-cell lung cancer
- Camrelizumab + rivoceranibApprovedHepatocellular carcinoma
- CemiplimabApprovedNon-small-cell lung cancerMelanomaPD-L1-high non-small-cell lung cancer without a driver mutation
- DostarlimabApprovedMismatch repair deficient (MSI-high) pancreatic ductal adenocarcinomaEndometrial cancerColorectal cancer
- IvonescimabApprovedNon-small-cell lung cancerColorectal cancerTriple-negative breast cancer (TNBC)
- NivolumabApprovedMelanomaNon-small-cell lung cancerRenal cell carcinoma
- PembrolizumabApprovedMismatch repair deficient (MSI-high) pancreatic ductal adenocarcinomaTriple-negative breast cancer (TNBC)Non-small-cell lung cancer
- +23 more at PD-1 →
- AK119Phase 2
- MavrostobartPhase 2
- EpacadostatNegative
How tumours escape
Records tied to this stage that describe resistance, evasion or tolerance. The resistance atlas lists the routes class by class.
- 2024rctNADINA: two doses of ipilimumab plus nivolumab before surgery beat a year of nivolumab after surgery in stage III melanomaNew England Journal of Medicinechanged practice
- 2024rctNICHE-2: a month of nivolumab and ipilimumab before surgery clears mismatch-repair-deficient colon cancer in most patientsNew England Journal of Medicinechanged practice
- 2024translationalNICHE-2: a single dose of ipilimumab and two of nivolumab before surgery clears dMMR colon cancer in most patientsNew England Journal of Medicinechanged practice
- 2023translationalRojas 2023: a personalised mRNA vaccine trained T cells against each patient's pancreatic cancer, and those who responded stayed cancer-free longerNature
- 2022rctCheckMate 816: three cycles of nivolumab plus chemotherapy before lung cancer surgeryNew England Journal of Medicinechanged practice
- 2022rctKEYNOTE-522: adding pembrolizumab before and after surgery in early triple-negative breast cancerNew England Journal of Medicinechanged practice
Measured by
Biomarkers, tests and assays in the corpus that read this stage in a patient.
Open questions
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.
- After IDO1 failed, which metabolic checkpoint (adenosine, arginase, lactate) is worth a phase 3?
- Can CAR-T cells be engineered to thrive in a nutrient-poor, acidic tumour?
- being tested at scaleresearchRandomised trials of stopping immunotherapy after one year versus continuing
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.
- early clinicalBiomarker-directed first-line quadruplets in gastric cancer
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.
- early clinicalBRAF/MEK plus PD-1 blockade as standard for BRAF-mutant anaplastic thyroid cancer
Add immunotherapy to the two targeted pills in the most aggressive thyroid cancer, because the combination has produced multi-year survivors in early series.
- early clinicalCD8 PET to stop or switch immunotherapy early
Scan for T cells inside the tumour a few weeks after starting immunotherapy. If they have not arrived, change course.
- early clinicalindustryClear the suppressive neutrophils out of pancreatic tumours first
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.
- early clinicalresearchConfirm ultra-low-dose immunotherapy so it can be afforded where most patients live
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.
- early clinicalresearchExtended-interval immunotherapy: give checkpoint inhibitors every 8-12 weeks once stable
Immunotherapy antibodies stay active in the body for weeks, yet are often given every two or three weeks. After a few months, spacing doses out to every two or three months might work as well, with fewer hospital visits and much lower cost.
- early clinicalGive immunotherapy in the morning
Several studies found patients infused with checkpoint inhibitors earlier in the day lived longer. If a randomised trial confirms it, it is a free improvement available everywhere tomorrow.
- early clinicalengineeringImplant a tiny device that tests twenty drugs inside the patient's own tumour
A rice-grain-sized implant releases microdoses of up to 20 drugs into separate spots of a tumour for one to three days, then is removed so pathologists can see which drug worked in that person's own tumour. First-in-human studies have been done in breast, sarcoma and brain tumours.
- early clinicalresearchLosartan to loosen the stroma of pancreatic cancer before chemotherapy: a phase 3
A cheap blood pressure drug may soften the dense scar tissue around pancreatic tumours so chemotherapy and immune cells can get in. Early trials look encouraging.
38 more ideas are linked to this stage's pathways, targets and terms; see the rankings →
Key evidence
Papers in the corpus tied to this stage's pathways, targets and terms, newest first.
- 2025rctCheckMate 067 at ten years: half of melanoma patients treated with nivolumab plus ipilimumab were alive a decade laterNew England Journal of Medicinechanged practice
- 2025rctCheckMate 067 at ten years: nivolumab plus ipilimumab produces long-term survival in half of patients with advanced melanomaNew England Journal of Medicinechanged practice
- 2025rctHARMONi-2: ivonescimab, a PD-1 x VEGF bispecific, beats pembrolizumab head-to-head in PD-L1-positive lung cancerThe Lancet
- 2024rctEV-302: enfortumab vedotin plus pembrolizumab replaces chemotherapy as first treatment for advanced bladder cancerNew England Journal of Medicinechanged practice
- 2024rctKEYNOTE-942: a personalised mRNA cancer vaccine plus pembrolizumab after melanoma surgeryThe Lancet
- 2024rctKEYNOTE-A18: pembrolizumab with chemoradiotherapy for locally advanced cervical cancer (overall survival)The Lancetchanged practice
- 2024rctKEYNOTE-A18: pembrolizumab with chemoradiotherapy for locally advanced cervical cancer (progression-free survival)The Lancetchanged practice
- 2024rctNADINA: two doses of ipilimumab plus nivolumab before surgery beat a year of nivolumab after surgery in stage III melanomaNew England Journal of Medicinechanged practice
- 2024rctNICHE-2: a month of nivolumab and ipilimumab before surgery clears mismatch-repair-deficient colon cancer in most patientsNew England Journal of Medicinechanged practice
- 2024translationalNICHE-2: a single dose of ipilimumab and two of nivolumab before surgery clears dMMR colon cancer in most patientsNew England Journal of Medicinechanged practice
- 2024rctSWOG S1826: nivolumab plus AVD chemotherapy versus brentuximab-AVD for advanced Hodgkin lymphoma in adolescents and adultsNew England Journal of Medicinechanged practice
- 2023rctNAPOLI-3: NALIRIFOX versus gemcitabine plus nab-paclitaxel as first treatment for metastatic pancreatic cancerThe Lancetchanged practice
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 5.6 of 56.