While immunotherapy is now a term many people are familiar with thanks to the continual promise it’s demonstrated for cancer treatment, the science behind why it works is often not communicated to the lay audience. This can make it challenging to understand the direction of current research studies and what these studies mean for colorectal cancer (CRC) patients. Recently, the American Association for the Advancement of Science published a study titled, “Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors.” It's important to understand the gut microbiome to improve immunotherapy outcomes for patients. The study investigated how the gut microbiome, which consists of all bacterial cells living inside the gastrointestinal tract, influences immune checkpoint inhibitors (ICIs), which are drugs such as Opdivo (Nivolumab) or Keytruda. More specifically, when the gut microbiome is out of whack and there is an imbalance of good bacteria vs. bad bacteria (which could be due to cancer itself, antibiotic use or other factors), the benefits of ICIs are not as noticeable.

What does this mean?

It’s important to first understand the immune response researchers studied. The immune response is comprised of T-cells, which are a type of white blood cell that help fight off infections and diseases. T-cells have receptors on their surfaces called PD-1 receptors, which can "turn off" the T-cells - stopping them from attacking other cells. Similarly, tumor cells have a protein on their surface called PDL1. When PDL1 proteins on the tumor bind to the PD1 receptor on the T-cell, the T-cell is not activated and so it doesn’t destroy the foreign cancer cells. Immune checkpoint inhibitor drugs (ICIs) work by releasing an immune response that blocks both the PDL1 protein on the tumor cell and the PD1 receptor on the T-cell so they can’t bind. When binding is prohibited, the T-cell is able to recognize the tumor cell as foreign and destroys it. Immune checkpoint inhibitors targeting this PD1-PDL1 interaction are a promising immunotherapy option for patients. Research studies are now showing however that individuals with an abnormal gut microbiome do not receive all the benefits from these types of treatment. This specific study demonstrated that antibiotics, which kill both good and bad bacteria in the GI tract, compromise the benefits of the PD1-PDL1 blockade process in both mice and humans, reducing the benefits from immune checkpoint inhibiting drugs.

How will this study affect future research and treatment?

Findings such as these are encouraging because they may offer alternative treatment options for colorectal cancer patients. One example is fecal microbiota transplantation (FMT), where the microbiome from a healthy individual is transplanted into the gut of an individual with an abnormal microbiome. The FMT from a healthy patient to an immunotherapy patient may improve the effects of ICI therapies by allowing T-cells to better target tumor cells. The research on gut microbiomes for cancer treatment doesn’t stop there. In addition to several new studies being released later this year, Dr. Cynthia Sears, an Infectious Diseases Specialist at Johns Hopkins and member of the Fight CRC/CRI Immunotherapy Work Group, has been leading innovative studies looking at how bacteria in the gut may play a role in the development of colorectal cancer and which bacteria stimulate immune responses leading to the progression of CRC.

"The emerging data that the microbiome may enhance ICI therapies is very exciting although there is still much to learn. Understanding which bacteria (gut bugs) may enhance specific therapies and cancers is the ongoing work at many places now." - Dr. Cynthia Sears

More:   Watch Dr. Sears give us a tour of her lab where she studies the gut microbiome!

Bringing Awareness to the Importance of Gut Microbiome

Dr. Sears and her team believe opening the doors to understanding immunotherapy in this light will help us find ways to block and control bacteria that contribute to CRC growth and, on the other hand, increase gut levels of those bacteria that help with CRC therapy. While the effects of a healthy gut microbiome are still being investigated, results from studies such as these are furthering research with the goal to prevent and treat colorectal cancer. Fight CRC will continue to be at the forefront of sharing the latest in research that is relevant and applicable to patients, survivors and caregivers. More:  A Blueprint to Advance Colorectal Cancer Immunotherapies published in Cancer Immunology Research

How Can You Help?

This year we funded a $400,000 research grant with our partners at Cancer Research Institute to study the gut microbiome and how it may impact immunotherapy. Help us fund another grant! Did you know 100% of the donations made to our Research Fund go directly toward this type of work? We need YOU to invest in colorectal cancer research! Learn about where our research funding goes, and check out the other scientists we've funded!

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FUNDING DISCLOSURE

Disclosure: Fight Colorectal Cancer has received funding from Merck Oncology, the producers of Keytruda® (pembrolizumab) and Bristol Myers Squibb (producers of Opdivo) in the form of unrestricted educational grants. We maintain ultimate authority over website content and the content written in this article. Fight Colorectal Cancer never recommends or endorses any specific physicians, products or treatments for any condition.

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