Over the past few years, scientists have come to a deeper understanding of how microorganisms can be seen as a major determinant of health and disease, including cancer.
The human body contains around 30 to 50 trillion bacteria, the microbiota, populating complex ecosystems called microbiomes in the skin, nose, mouth, stomach, and intestines. Some 99% of the microbiota in the human body reside in the gastrointestinal microbiome.
Gut Microbiota Shape Immune Response
Up to now, most oncology therapies have focused on killing cancer cells, through a variety of different approaches. However, increasing evidence has been documented that gut microbiota has an important impact in shaping systemic immune response.
A growing number of studies have revealed how gut microbiota change immune response and influence the efficacy of anticancer immunotherapeutics, e.g. anti-CTLA-4 and anti-PD-L1 antibody treatment, both in preclinical and clinical settings.
Response to Anti-PD-1 is Microbiome Modulated in Melanoma Patients
One recent clinical study reported that the composition of patient gut microbes appears to be a determining factor for immunotherapy response using an anti-PD-1 antibody in melanoma patients. Among the 93 patients treated with the anti-PD-1 immune checkpoint blockade, the researchers studied gut microbiome samples from 30 responders and 13 non-responders.
They found:
- A greater diversity of types of bacteria in the responders’ microbiomes.
- Increased abundance in responders of the Ruminococcaceae family of bacteria within the Clostridiales order.
- Increased abundance of Bacteriodales in non-responders and a much lower diversity of bacteria.
They also founded that responders had significantly increased immune infiltrates in their tumors, including the presence of CD8+ killer T cells, correlated to the abundance of a specific bacterium.
Utilizing the Microbiome as a Predictive Biomarker or Potential Cancer Treatment
These findings shed light on using the gut microbiome either as a biomarker to differentiate responders from non-responders in cancer immunotherapy, or as a potential alternative to cancer therapeutics.
In addition, with increased interest in how to transform non-responsive tumors to responsive tumors, future studies will explore combinations of immunotherapy and fecal transplantation as well as other strategies that may involve the use of antibiotics to selectively deplete certain bacteria or pre- or probiotic supplements to enhance certain bacteria into the gut.
Cancer Treatments can have a Negative Effect on Microbiota
Alternatively, chemotherapy and radiotherapy have detrimental effects on the gut-microbiota, leading to dysbiosis. Dysbiosis refers to a negatively altered microbiota, where symbiosis is affected. Immunotherapies also come with side effects, some of which lead to the development of colitis. Fecal transplant has been shown to be effective in treating inflammatory bowel disease and colitis.
Currently, in addition to augmenting immunotherapy efficacy, strategies are being aimed at restoring a balanced gut-microbiota via microbiota transplantation in order to mitigate side effects related to immunotherapy.
Profile the Microbiome to Potentiate Immunotherapy Response
To sum up, gut microbes could influence cancer outcomes through their interaction with host immunity. Profiling the individual’s gut microbiome needs to be further evaluated as a tool to potentiate immunotherapy response.
Further reading on the topic:
Zitvogel et al. Cancer and the gut microbiota: An unexpected link. Sci Transl Med. 2015; 7(271).
Roy and Trinchieri. Microbiota: a key orchestrator of cancer therapy. Nat Rev Cancer 2017; 17(5): 271-285.
Bhatt et al. The role of the microbiome in cancer development and therapy. CA Cancer J Clin 2017; 67(4): 326-344.
