2 min readFighting Cancer With Immunotherapy: Signalling Molecule Causes Regression of Blood Vessels, Study Finds

Berlin, Germany — Immunotherapy with T-cells offers great hope to people suffering from cancer. Some initial successes have already been made in treating blood cancer, but treating solid tumours remains a major challenge.

The signalling molecule interferon gamma, which is produced by T-cells, plays a key role in the therapy. It cuts off the blood supply to tumours, as a new study in the journal Nature reveals.

The immune system is the body’s most powerful weapon against diseases. So what if it were possible to use the immune system to fight cancer? For a long time now, researchers have been trying to do just that – for example, by employing a special kind of immune cell called T-cells. They are “special mobile forces” that – after undergoing training – patrol the body, and can seek out and kill cancer cells. This strategy has been successful in initial clinical trials – but mostly just in the treatment of cancers that do not form tumours, such as blood cancer.

Good at fighting blood cancer, but not so effective against solid tumours

Large solid tumours, on the other hand, sometimes pose big problems for T-cells. Though adept at targeting cancer cells swimming in the bloodstream, they have difficulty attacking compact tumours. The tumour weakens the aggressors through the delivery of inhibiting signals.

The scientists working with Dr. Thomas Kammertöns, Prof. Thomas Blankenstein, Prof. Hans Schreiber and Christian Friese are searching for solutions with their research team at Charité – Universitätsmedizin Berlin, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin Institute of Health (BIH) and the Einstein Foundation.

In a study published in the journal Nature, they investigated how the signalling molecules of T-cells affect the immediate tumour environment, which includes the connective tissue as well as the blood vessels that supply the tumour.

T-cells produce not only tumour necrosis factor (TNF) but also the molecule interferon gamma (IFN-γ). Until now, however, there has been little understanding about how IFN-γ really works. “We knew that IFN-γ attacks cancer cells via the tumour microenvironment,” says Kammertöns. “We now wanted to find out exactly which cells are targeted by the signalling molecules.”

Blood vessel regression is induced

The researchers generated genetically modified mice and used a clinically relevant cancer model. This included animals in which only blood vessel cells were susceptible to the signalling molecule.

In this mouse model IFN-γ pruned back the blood vessels in the tumours, thus shutting down the supply of oxygen and nutrients and killing the tumours. The researchers were able to observe this process microscopically in living mice in fine detail. They found that the blood vessel cells alone responded to the signalling molecule. When the researchers targeted other types of cells with IFN-γ, the tumours continued their growth.

These findings provided an explanation for the molecule’s powerful properties, which were already well known. “IFN-γ is one of the most important weapons in the T-cells’ arsenal,” says Thomas Kammertöns.

Thomas Blankenstein, lead investigator of the study, says: “The two together – IFN-γ and tumour necrosis factor – are a powerful team. TNF bursts tumour blood vessels, thus opening up the tissue, while IFN-γ cuts off the blood supply and keeps the tumour at bay over the long term.”

Optimizing T-cell therapy

The study offered the researchers clues on how to improve T-cell therapy for solid cancer tumours. Thomas Blankenstein explains: “We want to understand exactly how T-cells target tumours. Destroying a tumour’s infrastructure is probably more effective than killing individual cancer cells.”

“Our findings are significant beyond tumour therapy,” says Thomas Kammertöns. “Interestingly, the mechanism used by IFN-γ to eliminate solid tumours resembles the physiological regression of blood vessels during development. It also disrupts wound healing.”

“IFN-γ might also affect the formation of new blood vessels after strokes or heart attacks. That’s why we want to find out more about the molecular processes behind all of this.”

Article adapted from a Max Delbrück Center for Molecular Medicine in the Helmholtz Association news release.

Publication: Tumour ischaemia by interferon-γ resembles physiological blood vessel regression. Thomas Kammertoens et al. Nature (2017): Click here to view.

Cancer Immunotherapy

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