One of cancer’s crafty tricks involves manipulating the host’s immune cells to protect the tumors instead of fighting them. But now, researchers at Massachusetts General Hospital (MGH) have turned the tables around again, transforming these cells back into cancer killers.
In a fair fight between the immune system and cancer, the immune system would win most of the time. But cancer doesn’t fight fair – it uses a range of underhanded tricks to gain the upper hand. To promote its own growth, cancer creates its own microenvironment around it to sap nutrients and weaken the immune response in the area.
One of the most devious ways it does this is by hijacking the function of immune cells called regulatory T cells (Tregs). Normally these cells play an important role in keeping the immune system from attacking the body’s own cells, which would lead to autoimmune diseases. But some types of cancer will selectively let Tregs into their microenvironment, where they then fight off other immune cells that come to kill the tumor.
So for the new study, the researchers flipped this back on the cancer. They found a way to convert those Tregs into tumor-fighting T cells, which not only helps destroy the tumors from the inside out but allows other immune cells to chip in.
“Among elements of the tumor microenvironment, we exploited the preferential accumulation of Tregs in glioblastoma by therapeutically altering their function – a strategy known as reprogramming – to make them kill cancer cells instead of protecting them,” says Rakesh Jain, lead author of the study. “Because Tregs already present in these tumors can be reprogrammed, this strategy does not rely on additional recruitment of anti-tumor immune cells – another frequent barrier to successful immunotherapy in brain tumors.”
The team tested the technique on mice with human glioblastoma, a hard-to-treat form of brain cancer with a low survival rate. They used an antibody called αGITR, which worked to reprogram the cancer-defending Tregs into cancer-fighting CD4 effector T cells. This was backed up with existing drugs called immune checkpoint blockers (ICBs), which help boost the action of the immune system.
And sure enough, survival times in the mice were extended. In some cases, the tumors were not only eradicated completely, but when the scientists later reintroduced cancer cells into the mice, their immune system was still primed to fight them off.
As promising as the study sounds, it’s important to keep in mind that these results are so far only in mice, and may not necessarily carry across to humans. Further testing may open up new possibilities for using immunotherapy to treat brain cancers, which traditionally haven’t responded well to the technique.
The research was published in the journal Nature Communications.
Source: Massachusetts General Hospital
