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The Intestinal Microbiome and Cancer Immunotherapy

By Ryan M. Weight, DO, MS

Ryan Weight
Ryan Weight, DO, MS
Assistant Professor
Department of Medical Oncology
University of Colorado
Denver, Colorado

Ryan Weight, DO, MS, joined the University of Colorado School of Medicine faculty in 2019 as an assistant professor of medicine with a focus on the treatment of skin malignancies, including melanoma. Prior to this appointment, Dr. Weight served as an assistant professor of medicine at Thomas Jefferson University School of Medicine in Philadelphia.  In 2017, Dr. Weight was appointed leader of the cutaneous malignancy service line within the melanoma division of medical oncology. Dr. Weight established and served as co-director of the Complex Cutaneous Oncology Multidisciplinary Clinic in the Center for Heritable and Connective Tissue Skin Diseases, which brought together dermatology and medical oncology services for the treatment of dysplastic nevus syndrome, patients with a genetic predisposition to skin cancer, erythema bullosum, and others.

Dr. Weight has an interest in the management of immune-related adverse events caused by immune-activating therapies commonly used for the treatment of skin cancers. He served as director of the Immuno-Oncology Clinical Working Group at Thomas Jefferson University (2016- 2018), and as principal investigator for a number of clinical trials focused on the treatment of melanoma, including early phase trials. He has co-authored a multi-center adjuvant study of Nivolumab for the treatment of resected high-risk melanoma patients. 

  January 4, 2019

The human gastrointestinal tract is inhabited by a diverse population of bacteria that play a crucial role in maintaining homeostasis both within the gut and within the body. These various species of bacteria aid in the digestion and absorption of food products as well as functioning in less obvious roles such as protecting against invasive gastrointestinal infections and modulating the body’s natural immune system.

Recent advances in our understanding of the microbiome’s role in maintaining a balanced immune system has led to the suggestion that the bacterial makeup of the gut microbiome influences the effectiveness of immune checkpoint blockade drugs, which stimulate the immune system to treat cancer.

Research published in the journal Science by Routy et al. demonstrated that disruption of the gut microbiome through the use of antibiotics could alter the body’s response to certain immune checkpoint blockade drugs in patients with lung and kidney cancer. They went on to show that performing a fecal microbiota transplant (FMT), the process of transferring feces from one organism to another, using stool from a human patient with a “favorable” gut microbiota to a cancer-bearing mouse could effect the response of the mouse’s tumor to immunotherapy. Similarly, a second article published in Science by Gopalakrishnan et al. showed that patients undergoing treatment with immune checkpoint blockade for melanoma were more likely to respond to treatment if a certain bacterial species were present within the gut microbiota as well as if a more diverse bacterial population was present. Again, mice that received FMT from melanoma patients who responded to treatment had a higher likelihood of responding to immune checkpoint blockade drugs.

The results from these studies provide insight into the complex interplay between the body’s immune system and the bacterial makeup of the gastrointestinal tract. However, it is important to keep in mind that there are many factors that influence whether a tumor will respond or will not respond to immunotherapy. These findings do not suggest that antiobiotics should be avoided while receiving immunotherapy nor that fecal transplants are necessary for treatments to succeed. Additional research is needed to fully understand the effect of the microbiota on cancer and cancer treatment.

In my practice I recommend any person undergoing treatment with immunotherapy maintain a varied and well-balanced diet that includes leafy green vegetables, which tend to carry healthy bacteria that can be useful in maintaining a diverse gut microbiome. In the ever-changing landscape of medicine, there may be a time in the not-so-distant future when testing of a patient’s feces and medically manipulating the gut ecosystem will become a part of routine cancer care.