22 Mar UT Southwestern Lab Studies Interaction of Gut Microbiota and Cancer Immunotherapy

MedicalResearch.com Interview with:

Dr. Koh

Andrew Y. Koh, M.D.
Associate Professor, Pediatrics and Microbiology
University of Texas Southwestern Medical Center
Director of Pediatric Cellular and ImmunoTherapeutics Program
University of Texas Southwestern Medical Center and Children’s Health

MedicalResearch.com: What is the background for this study?

Response: We asked the basic question how does a bacteria in your gut help your immune system fight a cancer outside the gut (extraintestinal tumor).  Based on work that our group and others have published in the infectious diseases, microbiology, and inflammation fields, we knew that certain conditions (e.g. inflammation, infection) promote gut microbiota to move from the gut to the mesenteric lymph nodes.  So we hypothesized that immune checkpoint therapy (which essentially induces inflammation to promote tumor killing) might induce gut microbiota translocation to the mesenteric lymph nodes and that this might be the first step by which gut bacteria can engage with host immune cells. 

MedicalResearch.com: What are the main findings?

Response:  I think there are three major implications of our findings: 

1. There has been a lot of confusion and skepticism regarding the gut microbiome studies and cancer immunotherapy.  Why are different papers identifying/espousing different bacteria as being associated with positive clinical response in patients receiving ICT or as promoting anti-cancer immune responses in preclinical models.  The Gajewski group points to  Bifidobacterium spp.  The Zitvogel group likes Akkermansia muciniphila.  My group and Jenn Wargo’s group have pointed to Faecalibacterium prausnitzii.   So our study shows that many gut bacteria promote anti-tumor immune responses in the setting of ICT.  The bacteria just need to be able to translocate to secondary lymphoid organ and then have the capacity to activate the innate immune system (DCs) which than can enhance anti-tumor (Th1) adaptive immune responses.
2. The emerging concept of the tumor microbiome has also generated lots of skepticism.  How and why are bacteria in tumors that are very distant from the gut (e.g. melanoma, lung cancer, etc)?  Our study provides one potential mechanism by which tumor microbiomes can be established.
3. If translocation of gut bacteria to secondary lymphoid organs, including tumor draining lymph nodes, are required for optimal ICT efficacy, then this begs the question of whether gut microbiota can be delivered more directly to the tumor draining lymph nodes and tumors.  Perhaps giving live oral precision probiotics – which are fraught with many logistical challenges such as maintaining stable engraftment in the human gut which can easily be derailed by exposure to antibiotics or changes in diet – is not the best way to administer gut microbiota-based therapies.

MedicalResearch.com: How are gut bacteria altered?

Response:  We found that the gut bacteria are not significantly altered by the immune checkpoint blockade therapy in the melanoma model that we used.

MedicalResearch.com: What recommendations do you have for future research as a results of this study?

Response: Given the findings from our study, there may be ways to administer gut microbiota-based therapies outside the gut in a safe and reproducible manner.  There are ongoing efforts in my lab to do exactly that. 

I want to disclose that I am a consultant for Prolacta Biosciences.  I receive research funding from Prolacta Biosciences and Novartis.  I am co-founder of Aumenta Biosciences.

Citation:

Immune checkpoint blockade induces gut microbiota translocation that augments extraintestinal antitumor immunity

Last Updated on March 22, 2023 by Marie Benz