Microbiome metabolites may boost cancer immunotherapy effectiveness
It’s hard to overstate the incredible influence our gut microbiome has on our health. Now, researchers have found that certain metabolites from intestinal bacteria could boost the cancer-killing effect of immunotherapy.
Every person on Earth is carrying around trillions of microbes, the majority of which reside in our gut. This vast community has long been known to play a vital role in digestion and nutrient absorption, but more recent research has shown that it may influence the risk or severity of a range of conditions, including obesity, diabetes, Parkinson’s, Alzheimer’s, seizures, and even depression.
Cancer is another major disease that doesn’t escape the reach of the microbiome. In past research, scientists have found that different populations of microbes can affect the efficacy of certain cancer treatments called checkpoint inhibitors. Other studies found that a healthy microbiome gave the immune system’s natural killer cells a boost in fighting cancer, which could help improve the effectiveness of cancer immunotherapy.
And now a new study builds on that evidence. Scientists at the Universities of Würzburg and Marburg in Germany have identified metabolites from gut bacteria that seem to boost anti-tumor activity in immune cells. Specifically, they singled out two short-chain fatty acids called pentanoate and butyrate that could supercharge CD8+ T cells.
CD8+ T cells are immune system foot soldiers that specifically kill cells that, if left unchecked, would be dangerous for the body. One of their prime targets is cancer cells, but unfortunately the disease has a few ways to avoid detection. CAR T cell immunotherapy involves extracting these T cells from a patient, tweaking them to better target tumors, then returning them to the body to get to work.
In the new tests, the researchers performed that “tweaking” phase using pentanoate and butyrate, then set the newly boosted immune cells loose on solid tumors in a lab dish. Sure enough, the immune cells were much better equipped to attack the melanoma and pancreatic cancer cells.
"When short-chain fatty acids reprogram CD8 T cells, one of the results is increased production of pro-inflammatory and cytotoxic molecules," says Maik Luu, an author of the study. “The results are an example of how metabolites of intestinal bacteria can change the metabolism and gene regulation of our cells and thus positively influence the efficiency of tumor therapies.”
Currently, CAR T cell immunotherapy is most effective on blood cancers such as leukemia, and less so against solid tumors. But the success of the new study suggests that these kinds of fatty acids might be good candidates for treating T cells to target solid tumors.
There’s still plenty of work to do before then though, and the team says that the next steps involve looking at other cancer types that these fatty acids might work well against.
The study also hints at treatments for other diseases that might be hiding in that vast microbiome in our bodies.
The research was published in the journal Nature Communications.
Source: University of Würzburg