What is already known
Several studies have shown that gut microbes can sway responses to cancer immunotherapy — an approach that uses a person’s own immune system to kill tumor cells. However, the mechanisms behind these effects remain mysterious.
What this research adds
The commentary highlights a recent study that assessed the effects of antibiotics on clinical outcomes in cancer patients who received immunotherapy, and discusses it in the context of identifying microbial signatures to inform clinical strategies. Previous research has linked the presence of bacteria such as Bifidobacterium and Akkermansia muciniphila to increased response to immunotherapy and long-term survival. Cancer patients treated with broad-spectrum antibiotics and immunotherapy had a higher rate of disease progression compared with patients who took low-risk antibiotics or had no antibiotic exposure. Treatment with high-risk antibiotics reduced the abundance of gut microbes that produce the short-chain fatty acid butyrate and have been associated with favorable responses to immunotherapy.
Conclusions
Understanding how antibiotics influence the microbiota’s impacts on immunotherapy may inform strategies to identify cancer patients that are more likely to respond to cancer treatment.
Gut microbes can sway responses to cancer immunotherapy — an approach that uses a person’s own immune system to kill tumor cells. However, emerging evidence has shown that antibiotics can influence the microbiota’s impacts on immunotherapy.
Writing in Cell Host & Microbe, Yan Yan at the Chinese Academy of Sciences’ Key Laboratory of Molecular Virology and Immunology in Shanghai highlights a recent study that assessed the effects of antibiotics on clinical outcomes in cancer patients who received immunotherapy, and discusses it in the context of identifying microbial signatures to inform clinical strategies.
Immunotherapy has advanced the treatment of B cell malignancies and other cancers that do not respond to traditional therapies. “Although many patients initially responded to the therapy, only up to 40% of individuals can achieve durable remissions,” the author says.
Several studies have shown that specific gut microbes can boost responses to cancer immunotherapy. One unknown, however, is how the microbiota influences the immune system in ways that enhance such responses.
Antibiotics impact
Previous research has linked the presence of bacteria such as Bifidobacterium to long-term survival following cancer immunotherapy.
A recent study found that cancer patients treated with broad-spectrum antibiotics and immunotherapy had a higher rate of disease progression compared with patients who took low-risk antibiotics or had no antibiotic exposure. Treatment with high-risk antibiotics reduced the abundance of gut microbes such as Roseburia, Bifidobacterium and Lactobacillus species.
These microbes are known to produce the short-chain fatty acid butyrate and have been associated with favorable responses to immunotherapy.
Therapy response
The study also found that response to cancer immunotherapy was associated with a shift in gut microbes, including Bacteroides, Ruminococcus, Eubacterium and Akkermansia species. Akkermansia muciniphila has been previously linked to increased response to immunotherapy in epithelial tumors and with the production of immunomodulatory short chain fatty acids.
The findings offer insights into the importance of studying the effects of antibiotics on the microbiota’s impacts on immunotherapy, Yan says. However, he cautions, the results should be validated in larger clinical studies.
“Another potential complementary or alternative approach is the usage of bacteriophage therapy rather than broad-spectrum antibiotics to manipulate microbiota restoration,” the author says. Bacteriophages are viruses that infect and replicate within bacteria. “This strategy would more specifically reduce opportunistic pathogens and avoid the disturbance of beneficial bacteria.”
