Cold tumours and the immunosuppressive microenvironment

A powerful immune-suppressing signal called TGF-beta keeps immune cells out of tumours, but blocking it throughout the body causes heart and skin problems. Tethering the blocker inside the tumour could give benefit without the harm.

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.

An old part of the immune system called complement can be hijacked by tumours to summon protective cells. Drugs that block it already exist for other diseases.

Cancer cells can survive a drug because surrounding normal cells feed them growth signals. Blocking those signals could make existing drugs work better and longer.

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.

Tumours are acidic, and immune cells stop working in acid. Neutralising that acid, or blocking the pumps that create it, might let immunotherapy work.

Some cancer proteins sit on the cell surface or float outside cells, where protein-destroying drugs cannot reach. A different trick can drag them inside to be broken down.

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.

For people at very high cancer risk, install a small population of engineered immune cells that live for years and destroy cells showing early cancer signals before a tumour forms.

Tumours that contain small immune structures resembling lymph nodes respond far better to immunotherapy. Inducing those structures on purpose could make cold tumours responsive.

A rice-grain-sized implant can release small doses of many different drugs into separate spots of a tumour, then be removed so doctors can see which one worked in that person.

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.

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.

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.

The support cells that build a tumour's scaffolding come in several types: some protect the tumour, others restrain it. Treating all of them the same way explains past failures.

Focused ultrasound can break a tumour apart without heat or cuts, leaving debris the immune system can learn from. Doing that to one tumour may help treat the rest.

Interleukin-12 is one of the most powerful immune stimulants but is too toxic to inject into the bloodstream. A virus can be engineered to make it only inside a tumour.

Radiation can alert the immune system, but too big a single dose destroys the very alarm signal it creates. Picking the right dose and schedule may be free extra benefit.

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.

The liver is where bowel cancer most often spreads. Drugs delivered straight into the liver's blood supply could retrain its resident immune cells to reject arriving cancer cells.

Transferring gut bacteria from patients who responded to immunotherapy has helped some patients who had stopped responding. It is time for a proper large trial.

People who eat more fibre appear to respond better to immunotherapy, while some probiotic supplements may do the opposite. A proper trial would settle it.

Muscle is an immune organ as well as a movement organ. Building it during immunotherapy might improve how well the treatment works, not just how patients feel.

Certain vaccines and fungal sugars reprogramme the bone marrow so it produces more aggressive immune cells for months. That could be used before immunotherapy.

Intracavitary immunotherapy targets cancer that coats the lining of the abdomen or chest, which drugs given by drip barely reach. Delivering it straight into the cavity gives far higher local doses.

The first lymph node cancer reaches is also where the immune system learns to fight it. Injecting immunotherapy into that node before surgery, instead of removing it blindly, may work better.

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.

Low doses of drugs that change how DNA is packaged can make cancer cells display more of what marks them as abnormal, potentially waking up immunotherapy in cold tumours.

Tumours starved of oxygen produce a chemical that switches immune cells off. A scan can show which tumours are starved, and those are the ones to treat with blockers.

Low doses of anti-blood-vessel drugs briefly make tumour vessels work better, which helps immune cells and other drugs get in. Scans can find that window for each patient.