Effect of Microbiome on Colorectal Cancer Tumor Microenvironment

At the 2023 World Congress on Gastrointestinal Cancers, Rachel Purcell, PhD, BSc, MSc, University of Otago, Christchurch, New Zealand, presented study results on the influence the microbiome may have on the tumor-immune microenvironment in colorectal cancer.

Dr Purcell stated, "The main findings from our study are that the microbes within their tumor microenvironment really have a very profound effect on the immune response within those tumors," adding "although the microbes are few and not that abundant within the tumor microenvironment, they are tiny but mighty, and we ignore them at our peril."

Transcript:

Kia ora, hello. My name is Rachel Purcell and I'm from the University of Otago in Christchurch in New Zealand. I'm here at the 2023 World Congress on Gastrointestinal Cancers. I'm a research scientist. I run a research group in New Zealand, and our main focus is on the microbiome in colorectal cancer.

Now, a lot of us have heard a lot about the microbiome recently and its really important role in health and disease. And we've heard a lot about its role in cancer, how it affects how patients respond to therapies, and affects toxicity. Much of the research, that's been done in that space has mainly been looking at the gut microbiome, so the microbes in our colon, and how that affects different responses in the body in a more systemic way. But what we are really interested in is what actually happens in the level of the tumor.

Until quite recently, we didn't even realize that there was a tumor microbiome, but there's more and more evidence to show that this microbiome within the tumor itself has a really, really important role in disease progression and, potentially, also how those tumors respond to therapy. That's really our focus. My research mainly focuses on what's happening in the tumor microenvironment and, in particular, the tumor microbiome. Until recently, we didn't even realize how important that tumor microbiome is and how it might potentially affect the progression of tumors and also the response to therapy within the tumor.

We are taking a gene expression approach and looking at a large cohort of colorectal cancer tumors. We look at the microbial gene expression within the tumors, and we also look at the tumors themselves and the genes that they express. And we've devised this computational pipeline that allows us to look at both the microbes and what's happening on the host gene expression level and look for associations between the two.

What we found is by looking at consensus molecular subtypes of colorectal cancer, we found that the CMS1 and the CMS4 subtypes are quite highly immunogenic. But these 2 subtypes also have quite a high abundance of microbes within their tumor microenvironment. And we were able to actually drill down and look at the mechanisms of particular microbes in having an immunogenic effect within these 2 subtypes. Then what we were able to do was to take these ideas and bring it back to the lab and design some in vitro experiments using both colorectal cancer cell lines and immune cell cultures. And we were able to recapitulate what we actually see in the tumors of patients.

The main findings from our study are that the microbes within their tumor microenvironment really have a very profound effect on the immune response within those tumors. And, as we know, the immune response also has such a powerful impact on how patients respond to different types of therapies. I believe that although the microbes are few and not that abundant within the tumor microenvironment, they are tiny but mighty, and we ignore them at our peril.

Source:

Purcell R, Sulit A, Frizelle F, et al. The influence of the microbiome on the tumour-immune microenvironment in colorectal cancer. Presented at World Congress on Gastrointestinal Cancers; June 28-July 1, 2023; Barcelona, Spain. Abstract SO-23