The Influential Role of Gut Microbiome in Cancer Therapy

Gut feeling is more than just instinct. The microbes in the gut not only help digest food but also affect our ability to fight cancer, Dr. Jennifer Wargo explains.

By Sahana Shankar, Ph.D. Candidate

Thanks to the huge strides made by Immunotherapy in the past decade, today, we have quite a few successful therapies in the clinic that are specific and a less invasive alternative to chemotherapy. However, there are still some issues with toxicity, heterogeneous response, varied results based on timing, sequence, and combination of drug administration. Studies into the efficacy of immunotherapy show that response depends on tumor genome, epigenome, and microbiome, in addition to patient’s immunity and environment.

Dissecting the role of the microbiome in response to cancer immunotherapy, Dr. Jennifer Wargo, Professor at the MD Anderson Cancer Centre, University of Texas, shared some insights at BIO Asia-Taiwan 2020, on how the internal microbiome could be used to understand, diagnose and improve immune response to cancers.

For over a century, there has been evidence of microbes in human tumors and their ability to impact therapy. So far, 16% of human cancers could be related to microbes. In her previous work at Harvard University, Dr. Wargo demonstrated that bacteria in pancreatic tumors in mice could break down the chemotherapeutic agents and reduce the efficiency of immunotherapy. Others have shown that some bacteria positively affect therapy response. Hence, they can serve as valuable biomarkers and potential therapeutic targets.

Speaking specifically of the gut microbiome, landmark studies have shown that it could alter the response to immunotherapy. The diversity and composition of gut microbiome contributed to differential responses to drugs in mice models. High diversity and the presence of specific bacteria are indicators of a positive immune response.

Dr. Wargo shared her work on the analysis of oral and gut microbiome before and after therapy in metastatic melanoma by microbiome sequencing and immune profiling. Results suggest that a higher diversity correlates to a better response to the anti-PD1 blockade. Responders had a higher abundance of certain families of bacteria, which could act as ‘favorable signatures’ associated with better immune response.  Analyzing the immune cells in responders and non-responders showed higher expression of cytolytic T-cell markers such as CD80. Microbiome from responders and non-responders injected into mice with tumors indicated that fecal transplants from non-responders resulted in the rapid growth of the tumor in mice with a resistance to the immune checkpoint blockade. In contrast, a fecal transplant from responders allowed the mice to respond well to the cancer immunotherapy.

Clinical trials are underway at MD Anderson Cancer Centre to show that the response of patients on anti-PD1 therapy could be modulated by fecal transplants with microbiome with favorable signatures, suggesting that altering the gut microbiome is a viable option to improve immune response during cancer therapies. Diet and lifestyle are other factors that alter the microbiome’s response to drugs.

Apart from the microbiome, there could be several other factors that could impact cancer immunotherapy and can be modulated to improve efficacy. Dr. Wargo shared some data on how antibiotics could negatively affect response to anti-PD1 therapy. Overall, her talk stressed the need for new biomarkers and targets that indicate internal and external factors contributing to carcinogenesis and response to treatment. This could be made possible by a comprehensive and organized approach to dissect cancer immunotherapy.

Editor: Rajaneesh K. Gopinath, Ph.D.

Related Article: AACR 2020: Modifications in Tumor Microenvironment and Host Microbiome, a Potential Therapeutic Strategy for Immunotherapy

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