Immune attack! –
We don’t know enough to know whether this is useful yet.
John Timmer – Jan , (6:) (pm UTC )
Despite these successes, many patients aren’t helped by the newer immune-focused therapies, raising questions of what else we still need to figure out to help cancer patients. A new paper highlights something we may have missed: a class of immune cells that appears to be primed specifically to attack cancer. But the finding raises questions about what it is on cancer cells that the immune cells are recognizing and why they fail to keep cancer in check.
Finding cancer killers
The start of this work was pretty simple: a large international team of researchers grew a mix of immune cells called “T cells” in the presence of cancerous cells and looked for cells that grew rapidly. This rapid growth is typically a sign that the immune cells have been activated by something they recognize — in this case, the cancer. They identified one particular lineage of T cells that grew well and named it MC.7.G5, confirming yet again that most scholars don’t belong in the creative industries.
One notable thing about the MC.7.G5 cells quickly became apparent: MC.7.G5 did simply grow well in the presence of cancer cells; it killed them. So, the authors tested a variety of different cancer types (lung cancer, melanoma, colon, breast, and more). These cells don’t have much in common. They’re activated by different mutations, start out with different populations on their surface, and have many other differences from one another. So it was not clear what the T cells could possibly be recognizing on their surfaces in order to attack them.
To find out, the researchers did an experiment that wouldn’t have been possible just a decade earlier: they used a gene- editing construct to eliminate every single protein-coding gene that we know of in the genome. Plenty of individual populations of a cancer-cell line had a single gene knocked out and then were tested to see whether the MC.7. G5 immune cells could still kill them. If any cancer cells were left alive, then the gene edited in them would be essential for producing the molecule used by the immune cells to recognize cancer.
The experiment identified a series of genes involved in putting a single protein on the surface. But, of course, that protein is also present on normal cells. How could it possibly be responsible for the cancer cells being recognized as distinct?
Fortunately, we know a lot about the family of molecules that the protein, MR1, belongs to, as well as a bit about MR1 itself. The larger family includes the molecules that help the immune system recognize self from non-self by binding to bits of the cell’s proteins and presenting them on the cell’s surface for the immune system to check out. If either these molecules or the proteins they present look different, the immune system attacks. So, that makes a degree of sense as something that can trigger the immune system to go after the cancer cells.
MR1, however, does work like that. Instead, it brings some of the cell’s metabolites to the surface. And the researchers confirmed that it has to bind to something in order to make it to the surface. They hypothesize that it’s a metabolite that’s specific to cancer cells, but they have no idea what it might be.
Stay on target
While there are still some question marks about what causes these immune cells to pick out cancerous cells, there’s no shortage of evidence that they do so effectively. The researchers tested the immune cells against resting and dividing normal cells and got no response. MC.7.G5 did not kill healthy cells that were stressed or damaged. So, there’s no indication that the immune cells accidentally go off target and kill healthy cells.
The researchers also confirmed that the cancer-killing T cells are defined by the standard receptor that T cells normally use to recognize infected cells . They made a copy of this receptor’s genes and inserted them into T cells from an unrelated individual. They also killed cancerous cells from at least two different sources.
Finally, the authors injected lymphoma cells into immune-compromised mice, then added the cancer-killing T cells. In control mice without the cancer-killing cells, the lymphoma took over the bone marrow, eventually accounting for about 80 percent of the cells there. With the cancer-killing cells injected at the same time, the bone marrow in the mice consistently had far fewer cancer cells (consistently less than (percent of the total cells). This indicates that the immune cells can help keep cancer in check but may not be able to consistently eradicate it.
Does that mean, as the
BBC has claimed , that these cells “May treat all cancer”? Well, to begin with, the T cells were seemingly unable to eliminate cancer in mice. That’s more significant than it seems, in that lots of potential treatments seem to work well in mice, but a few ever advance to the point of clinical trials in humans, much less end up being used as treatments. This is a case when mouse assays are helpful for knowing what deserves a closer look but far from the last word on a topic.
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