Microbes Interfere with Cancer Treatment

First-in-Human Clinical Trial: Can Gut Microbes Interfere with Cancer Treatment?

In recent years, researchers around the world have shown that the gut bacteria of cancer patients may yield essential information for improving the efficacy of cancer therapies. These findings appear to be linked with the capability of gut bacteria, also known as the gut microbiome, to boost the immune system.

The vast collection of microorganisms that live in the gastrointestinal tract make up the gut microbiome. Recent studies suggest that these varied microbes may play a critical role in helping patients respond to a particular type of new drug – immune checkpoint inhibitors. These immunotherapy drugs help immune cells to recognize and attack tumor cells. Scientists at the University of Pittsburgh and at Sheba Medical Center, respectively, are conducting unique clinical trials to test whether the gut microbiome has a significant impact on the effects of immunotherapy when treating advanced cases of cancer.

Due to the overproduction of certain proteins (such as PD-L1), cancer cells are able to hide from immune cells, thereby avoiding the natural anti-cancer responses of the immune system. As a result, the immune system fails to eradicate these cells. However, decades of research show how PD-1 and PD-L1 inhibitors can prevent the interaction between the protein on the cancer cell and the receptor on the body’s immune cells. Consequently, the immune system is able to recognize and kill the cancer cells.

These breakthrough research studies facilitated the development of drugs such as PD-1 and CTLA-4 inhibitors, which trigger the body’s immune system to release large quantities of T-cells that target and destroy cancer cells. In effect, these drugs produce long-lasting responses that change certain cancers into a chronic disease. However, the drugs are not effective for all types of cancer or for all patients.

According to research by several institutions, such as the MD Anderson Cancer Center, Gustave Roussy, the University of Chicago, and the University of Texas, not having the correct gut microbes may be the reason why PD-1 inhibitors do not work for all cases of cancer. The first-in-human trials are now analyzing the connection between the gut microbiome and cancer treatment.

These early trials involve taking fecal samples from patients who have experienced a positive response to anti-PD-1 immunotherapy. The gut microbes of these samples are then used to create a fecal microbiome transplant (FMT). Patients with cancers that have not responded to anti-PD-1 immunotherapy are given a PD-1 inhibitor drug (pembrolizumab) along with an FMT via a colonoscopy. If patients respond to this therapy, then they continue to receive the drug over a two-year span.

Studies on whether this manipulation of the microbiome can treat advanced melanoma are ongoing. The results are promising and scientists are working to uncover new links between people’s intestinal microbiome and their response to immunotherapy cancer treatment.