Gut bacteria affect response to cancer therapy

07 November 2017

Interview with

Jennifer Wargo and Deepak Gopalakrishnan, University of Texas

Whether a cancer victim responds to certain treatments or not might be dictated by the bacteria they carry in their intestines,  according to a new study from researchers at the University of Texas. Jennifer Wargo and Deepak Gopalakrishnan looked at more than 100 patients with the skin cancer “melanoma”. Those that responded best to a therapy designed to make the immune system attack tumours had a very different spectrum of gut microbes compared with patients who responded less well. And the same bacteria produced similar outcomes in mice with tumours as well, as Chris Smith found out…

Jennifer - We wanted to focus on an area that there’s a growing interest in and that’s the microbiome. We know that in our bodies we have trillions of bacteria; they actually outnumber our own normal cells by up to ten to one. And it’s becoming quite apparent that these bacteria can actually influence how our body functions, not only from a digestion standpoint but they can actually influence our own immune system. So we studied a large group of patients with metastatic cancer, cancer that had spread throughout the body. In this case, metastatic melanoma which, again, is a form of skin cancer.

Chris - But Deepak, what did you actually do? How did you do the experiments?

Deepak - We started enrolling patients in our protocol about 2/2½ years ago. Before they started therapy we started to collect an oral and a gut microbiome sample from them in order to identify what bacteria are present and the diversity of the communities, as well as the component bacteria within each of the communities. We also looked at the response of these patients in order to correlate whatever microbiome characteristics we had identified with response.

Chris - Right, so you’ve got a group of patients; they’re united by having malignant melanoma, a kind of skin cancer that’s spread around their body and they’re receiving immunotherapy which encourages the immune system to hit their cancer, and you’re saying in these people who responded to this, are there any differences in the bugs they have in them compared to people who do less well?

Jennifer - That’s correct.

Chris - What did you find?

Jennifer - We didn’t see any substantial difference when we looked at the bacteria in the mouths of these patients, but we did find night and day differences in the gut microbiome of these patients - with patients who responded to the immunotherapy having higher diversity of bacteria within their gut, and also different bacteria, specifically more bacteria in something called the ruminococcus groups.

Chris - Why do you think, Deepak, that the difference in the bugs makes a difference to the response to therapy? What do you think’s going on?

Deepak - That’s a very fascinating question and we are also trying to better understand the mechanism that is driving these responses. One of the primary reasons is that the gut is a seat of high immune activity within the body, and there is plenty of scope for interaction between the microorganisms that inhabit the gut and the immune systems. There is a lot of interfacing between these two processes that takes place at the gut.

We also took our study into mice. What we did was we took germ free mice so these did not have any microbiota in their intestine and we transplanted them with a stool from either a patient who responded very well on therapy versus a patient who did not respond at all. And there we saw that mice that received the responder’s stool, they grew much smaller tumours and did much better on therapy compared to mice that received non-responder stool.

Chris - Would you speculate then that in a person with melanoma, if they have a certain spectrum of bacteria living in their intestines, these are in some way manipulating the immune system and putting it into a state that determines how well it will attack a tumour if given a chance?

Jennifer - That’s absolutely what we think. I think in our body there’s certainly the highest density of bacteria within our gut and they’re constantly interacting with the immune cells that are also in our gut and surround our gut. So it’s essentially shaping an immune response in normal healthy people as well as in patients with cancer.

Chris - Do you think that there might even be grounds, in the future, for carrying out a selective transfer of faecal bacteria into cancer victims in order to better stimulate their immune responses?

Jennifer - Absolutely. This approach is already being used for non-cancer states like clostridium difficile colitis, or infections of the colon, and also for inflammatory bowel disease where you can actually do as you say a transfusion or a faecal transplant. Certainly, I think the concept for treating patients with cancer using faecal transplant and other strategies to change the microbiome is very real. In fact, we’re planning a study to do just that, to try and change the microbiome and hopes to improve the responses to immunotherapy.

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