4 ms·

Gut Microbes Can Shape Responses to Cancer Immunotherapy

84 points by daegloe 9y ago

feelix 9y ago
Does anyone have any theories as to how this may work, assuming that it's not a case of correlation does not equal causation?
- Mz 9y ago
  The gut contains about 70 percent of your immune cells. Biofilms are a situation where infection essentially terraforms the body. I think it is a bit like how some plants grow in deserts and others grow on swamps, but larger forces determine what is desert and what is swamp.
- roberte3 9y ago
  One of the things that came up at a recent kidney cancer seminar I attended, is that they are seeing better immune response with a more diverse gut biome. The University of Washington researchers weren't willing to give medical advice, but they were very pro- immune treatment patients taking probiotics. They are still a few years out from publishing.
- josephst18 9y ago
  Theory/ educated guess: these therapies try to antagonize the PD1 receptor, which is found on immune cells (specifically, T cells); in a healthy individual, the binding of PD-1L to PD-1 provides a "don't kill me" signal so that the body's own cells are not destroyed by the immune system. The problem with this is that cancers frequently develop mutations and overexpress PD-1L which prevents the immune system from properly targeting them for destruction. These anti-PD1/ anti-PD1L try to counteract this overexpression, allowing the immune system's T cells to destroy the cancer. However, targeting the cancer requires a functional immune system; this is where the gut microbiome comes in. It's a sort of "home gym" for the immune system--having a diverse range of bacteria helps keep the immune system strong; gnotobiotic mice (mice bred and raised in completely germ-free environment without any gut microbes) have significantly weakened immune systems. So theory is that the gut microbiome acts as a "home gym" where the immune system can "train". Anything that reduces gut microbiome (such as antibiotics) will also reduce this "training" and leave the immune system less able to apply its training to fighting off cancer cells.
boyd 9y ago
Here are the links to the study (missing from the Scientific American article but in the original): - Gut microbiome modulates response to anti–PD-1 immunotherapy in melanoma patients http://science.sciencemag.org/content/early/2017/11/01/science.aan4236.full http://science.sciencemag.org/content/early/2017/11/01/scien... - Gut microbiome influences efficacy of PD-1–based immunotherapy against epithelial tumors http://science.sciencemag.org/content/early/2017/11/01/science.aan3706.full http://science.sciencemag.org/content/early/2017/11/01/scien... Here is some earlier (cited) work in mice that very strongly showed an effect between this therapy and the mouse gut microbiome (Commensal Bifidobacterium promotes antitumor immunity and facilitates anti–PD-L1 efficacy): http://science.sciencemag.org/content/early/2015/11/04/science.aac4255.full http://science.sciencemag.org/content/early/2015/11/04/scien.... Really interesting to see these finding preliminarily reproduced in a clinical setting.
- AlexCoventry 9y ago
  Do you have the DOIs for the supplementary materials available?
arca_vorago 9y ago
I was privileged to get to sysadmin for a pioneer microbiologist-geneticist whose passion was the microbiome. Not long before I left, I started seeing indicators that the the microbiome(s) in us and that we encounter and how they interact is vastly more important than we have realized. From this biofilms have made advances, etc. With sequencing getting so much cheaper, the research opportunities are just sitting around waiting, and are the kind that offer real and tangible results.
- vvdcect 9y ago
  What are the types of food that one could take to improve or help our gut microbes?
  - CuriouslyC 9y ago
    Beans are the best, as they have the highest percentage of fermentable fiber in the form of raffinose. Pectin in apples, pears and citrus, the beta-glucan in oats and barley, and inulin in alliums, chicory and jerusalem artichoke are all good as well. To get the most benefit, pair your fiber source with a probiotic food. Good examples are unpasteurized sauerkraut, kimchi, yogurt, kefir, etc.
  - mariushn 9y ago
    From https://www.juvmed.com/healthy-diet https://www.juvmed.com/healthy-diet Beans, lentils and chickpeas Wholegrain and wholemeal, bran based cereal, oatmeal Brown or wholegrain rice Broccoli, artichoke, avocado, brussels sprouts Raspberries, pear, apples Chia seeds

84 points by daegloe 9y ago

Does anyone have any theories as to how this may work, assuming that it's not a case of correlation does not equal causation?

Mz 9y ago
The gut contains about 70 percent of your immune cells. Biofilms are a situation where infection essentially terraforms the body. I think it is a bit like how some plants grow in deserts and others grow on swamps, but larger forces determine what is desert and what is swamp.
roberte3 9y ago
One of the things that came up at a recent kidney cancer seminar I attended, is that they are seeing better immune response with a more diverse gut biome. The University of Washington researchers weren't willing to give medical advice, but they were very pro- immune treatment patients taking probiotics. They are still a few years out from publishing.
josephst18 9y ago
Theory/ educated guess: these therapies try to antagonize the PD1 receptor, which is found on immune cells (specifically, T cells); in a healthy individual, the binding of PD-1L to PD-1 provides a "don't kill me" signal so that the body's own cells are not destroyed by the immune system. The problem with this is that cancers frequently develop mutations and overexpress PD-1L which prevents the immune system from properly targeting them for destruction. These anti-PD1/ anti-PD1L try to counteract this overexpression, allowing the immune system's T cells to destroy the cancer. However, targeting the cancer requires a functional immune system; this is where the gut microbiome comes in. It's a sort of "home gym" for the immune system--having a diverse range of bacteria helps keep the immune system strong; gnotobiotic mice (mice bred and raised in completely germ-free environment without any gut microbes) have significantly weakened immune systems. So theory is that the gut microbiome acts as a "home gym" where the immune system can "train". Anything that reduces gut microbiome (such as antibiotics) will also reduce this "training" and leave the immune system less able to apply its training to fighting off cancer cells.

boyd 9y ago

Here are the links to the study (missing from the Scientific American article but in the original): - Gut microbiome modulates response to anti–PD-1 immunotherapy in melanoma patients http://science.sciencemag.org/content/early/2017/11/01/science.aan4236.full http://science.sciencemag.org/content/early/2017/11/01/scien... - Gut microbiome influences efficacy of PD-1–based immunotherapy against epithelial tumors http://science.sciencemag.org/content/early/2017/11/01/science.aan3706.full http://science.sciencemag.org/content/early/2017/11/01/scien... Here is some earlier (cited) work in mice that very strongly showed an effect between this therapy and the mouse gut microbiome (Commensal Bifidobacterium promotes antitumor immunity and facilitates anti–PD-L1 efficacy): http://science.sciencemag.org/content/early/2015/11/04/science.aac4255.full http://science.sciencemag.org/content/early/2015/11/04/scien.... Really interesting to see these finding preliminarily reproduced in a clinical setting.

AlexCoventry 9y ago
Do you have the DOIs for the supplementary materials available?

arca_vorago 9y ago

I was privileged to get to sysadmin for a pioneer microbiologist-geneticist whose passion was the microbiome. Not long before I left, I started seeing indicators that the the microbiome(s) in us and that we encounter and how they interact is vastly more important than we have realized. From this biofilms have made advances, etc. With sequencing getting so much cheaper, the research opportunities are just sitting around waiting, and are the kind that offer real and tangible results.

vvdcect 9y ago
What are the types of food that one could take to improve or help our gut microbes?
- CuriouslyC 9y ago
  Beans are the best, as they have the highest percentage of fermentable fiber in the form of raffinose. Pectin in apples, pears and citrus, the beta-glucan in oats and barley, and inulin in alliums, chicory and jerusalem artichoke are all good as well. To get the most benefit, pair your fiber source with a probiotic food. Good examples are unpasteurized sauerkraut, kimchi, yogurt, kefir, etc.
- mariushn 9y ago
  From https://www.juvmed.com/healthy-diet https://www.juvmed.com/healthy-diet Beans, lentils and chickpeas Wholegrain and wholemeal, bran based cereal, oatmeal Brown or wholegrain rice Broccoli, artichoke, avocado, brussels sprouts Raspberries, pear, apples Chia seeds