- There is a growing interest among cancer patients in using probiotics to improve their health, but it remains unclear how gut microbes alter cancer immunotherapy responses.
- Now, researchers have shown that, in mouse models, probiotics, or “good” bacteria, Lactobacillus roteri It translocates to melanoma tumors, where it enhances antitumor immunity and facilitates cancer immunotherapy by releasing indole-3-aldehyde (I3A).
- They also found that patients with advanced melanoma who responded to immunotherapy had higher I3A levels compared to patients who did not respond.
- More studies are needed, but researchers hope these findings will pave the way for diet- and probiotic-based cancer treatments.
In recent years, there has been remarkable progress in the field of cancer immunotherapy. This powerful cancer treatment strategy works by harnessing an individual’s own immune system to recognize and destroy cancer cells.
Currently, immunotherapy
Scientists are trying to discover why people respond differently to this type of cancer treatment.
One factor that may be responsible for the altered response to immunotherapy is the gut microbiome — or the many microbes in the gut — which scientists think may play a role in the body.
Researchers have found that some gut bacteria may modulate the activity of immune cells, while others may alter the effectiveness or toxicity of certain drugs.
The gut microbiome varies greatly from person to person. Although individual humans are 99.9% identical to each other in terms of DNA, they can also be
It could be the gut microbiome
Now, a new study from the University of Pittsburgh, Pennsylvania, has investigated the effect of probiotics on immunotherapy response for melanoma. Their results appear in the journal
Dr. Marlisse Meisel, first author of the study and assistant professor in the Department of Immunology at the University of Pittsburgh, said, Medical news today:
Cancer patients, including those undergoing treatment with immune checkpoint inhibitors (ICI), are increasingly consuming probiotic bacteria. Probiotics have been found to influence responses to ICI treatment in melanoma. However, the mechanisms of how gut probiotics shape systemic tumor immunity and thus modulate ICI efficacy remain poorly understood. Thus, we set out to test the role of four commonly used probiotic bacteria, incl Lactobacillus roteri. “
Many types of cancer prevent the body’s immune cells from attacking and killing tumors.
In 2011, the Food and Drug Administration (FDA) approved the use
Ipilimumab was the first in a class of drugs known as
ICIs work by blocking certain proteins, such as CTLA-4, PD-1, and PD-L1, that can stop cancer-killing T cells in the body. By blocking these proteins, ICI helps T cells attack and destroy cancer cells.
ICIs have shown promising results in
To understand how probiotics alter the effectiveness of ICI, the Pittsburgh researchers first had to identify which gut bacteria are able to suppress tumor growth.
The researchers orally administered four types of commensal or “good” bacteria to mice with melanoma: Bifidobacterium longumAnd Lactobacillus roteriAnd Lactobacillus JohnsonAnd Escherichia coli.
They chose these bacteria because they are often used as probiotics and are found in high amounts in the gut microbiomes of melanoma patients who respond well to ICI treatment.
The researchers found that giving mice the lungsAnd colior L. reuteri On a daily basis, starting 1 day after subcutaneous transplantation of B16-F0 tumor cells, it effectively slowed melanoma growth and increased survival rates.
L. johnsonii It didn’t have the same effect.
L. reuteri It was most effective in suppressing tumors compared to the other two bacteria and the control group.
The next step was to investigate the mechanism by which L. reuteri Limits the growth of skin cancer.
The researchers found that L. reuteri It travels to melanoma tumors, colonizes them, and persists within them.
in the tumor L. reuteri Dietary tryptophan, an essential amino acid found in protein from plant and animal foods, is metabolized to indole-3-aldehyde (I3A).
I3A activates the aryl hydrocarbon receptor (AhR) within CD8 T cells, which stimulates the production of interferon-gamma by these cells.
The researchers next examined the clinical significance of their mouse model’s findings in a cohort of patients with advanced melanoma who had either a positive or negative response to intrauterine injection therapy.
“Excitingly, we found that melanoma patients who responded to ICI had elevated levels of I3A in contrast to patients who did not,” Dr. Meisel told us.
“Higher levels of I3A before treatment were also associated with a better chance of survival,” she added.
Another mouse melanoma model study published in March 2023 showed a positive correlation between the gut microbiome and the effectiveness of cancer immunotherapy.
That study concluded that ICSI treatment leads to inflammation in the gastrointestinal tract, allowing bacteria to move from the intestines to lymph nodes close to tumors, where immune cells are activated.
However, A.J
said Dr. Maisel MNT Their study “provides a rationale for evaluating the antitumor effect of this novel diet and probiotic-based therapeutic strategy in clinical trials in cancer patients.”
However, more research is needed to determine, first, how many different species of tryptophan-derived bacteria that release the AhR ligand use this mechanism, and second, whether a tryptophan-rich diet leads to more bacteria producing AhR ligands and an immune response. Better in CD8 T cells.
The study authors would also like to go further and investigate how exogenous, exogenous, endogenous, or endogenous activation of AhR affects tumor immunity in melanoma, and whether I3A could help patients with other types of ICI-resistant cancers.