Gut microbiome modulates response to anti–PD-1 immunotherapy in melanoma patients

[D.ap]

Preclinical mouse models suggest that the gut microbiome modulates tumor response to checkpoint blockade immunotherapy; however, this has not been well-characterized in human cancer patients. Here we examined the oral and gut microbiome of melanoma patients undergoing anti–programmed cell death 1 protein (PD-1) immunotherapy (n = 112). Significant differences were observed in the diversity and composition of the patient gut microbiome of responders versus nonresponders. Analysis of patient fecal microbiome samples (n = 43, 30 responders, 13 nonresponders) showed significantly higher alpha diversity (P < 0.01) and relative abundance of bacteria of the Ruminococcaceae family (P < 0.01) in responding patients. Metagenomic studies revealed functional differences in gut bacteria in responders, including enrichment of anabolic pathways. Immune profiling suggested enhanced systemic and antitumor immunity in responding patients with a favorable gut microbiome as well as in germ-free mice receiving fecal transplants from responding patients. Together, these data have important implications for the treatment of melanoma patients with immune checkpoint inhibitors.


https://scholar.google.com/scholar?q=im ... JFklO9CRUJ

[Olga]

Yes Deb, we have already discussed this subject before and this is one more supporting article. But people have to understand, that:
1. They might already have a very good microbiome to start from, at the start of their anti-PD-1 therapy. Do not assume it is poor, unless you just had the treatment with antibiotics or the radiation to abdomen. Trying to fix what is already pretty good might harm this delicate community in your gut. Wait till the few scan results to decide if you need to try to do something to your microbiome.
2. Do not try to fix it with the supplements. There are no pills of any kind that that can give you the best gut composition from the immunotherapy point of view. You can even harm you microbiome if huge doses of the chosen culture is forced into your gut microbiome community.
3. I would say - just feed them well. Make your gut community your favorite pets. They like plant based foods with the insoluble fiber - so after it passes the stomach community, there is something left for the ones in the gut - unrefined grains, seeds from the berries, skin from the grapes etc. Eating food cold makes more of it pass to the lower parts without being totally digested in the upper parts.
4. Fecal transplant is really being overlooked as a fix. It is hard to get, but there are few gut diseases esp. in the kids that some parents succeeded in making it work for them. If the immune-therapy is not working for you, look into this.

[D.ap]

Thank you Olga ,

It’s all very very good advice .

I wonder if folks who have been disqualified from trials (ie colitis and pneumonitis) could be reintroduced to immunotherapies after they’ve been determined to have a better gut microbe by way of testing ?

I wonder if the test ( fecal) should be as important as testing for Pd1 content ?
Could you remind me why we look to melanoma as a comparable to alveolar soft part sarcoma ? Is it the TFE3 translocation similarity ?

[D.ap]

Any thoughts from anyone ?

[D.ap]

Yes Deb, we have already discussed this subject before and this is one more supporting article. But people have to understand, that:
1. They might already have a very good microbiome to start from, at the start of their anti-PD-1 therapy. Do not assume it is poor, unless you just had the treatment with antibiotics or the radiation to abdomen. Trying to fix what is already pretty good might harm this delicate community in your gut. Wait till the few scan results to decide if you need to try to do something to your microbiome.
2. Do not try to fix it with the supplements. There are no pills of any kind that that can give you the best gut composition from the immunotherapy point of view. You can even harm you microbiome if huge doses of the chosen culture is forced into your gut microbiome community.
3. I would say - just feed them well. Make your gut community your favorite pets. They like plant based foods with the insoluble fiber - so after it passes the stomach community, there is something left for the ones in the gut - unrefined grains, seeds from the berries, skin from the grapes etc. Eating food cold makes more of it pass to the lower parts without being totally digested in the upper parts.
4. Fecal transplant is really being overlooked as a fix. It is hard to get, but there are few gut diseases esp. in the kids that some parents succeeded in making it work for them. If the immune-therapy is not working for you, look into this.

[Olga]

It is really hard to find a reliable local way to test your gut microbiome. Some important bacteria are anaerobic and will die if free oxygen is present so even if you obtained the proper kit for testing (as we did and it was not easy to get) the chances you are able to collect what was produced without any exposure to the air are slim. I know that people have had success in treating their kids colitis by their own fecal transplant but in that case they do not need any quantification just hoping that at least some microbiome survives and colonizes the kids gut.
Ivan said in China people can have a fecal transplant at the clinics if they pay. I have seen the same in Oregon, but it might be limited, I do not know. If Ivan had no response, I would not hesitate to make my own fecal transplant though.

[D.ap]

Olga
How will a base line be established ?
Or is that necessary ?
Jussi ?

[D.ap]

“Fecal Transplant Heals Colitis Caused by Immunotherapy

A case study of two patients with advanced cancer shows it might be possible to avoid a common and severe side effect of immunotherapy treatment.”


https://www.the-scientist.com/news-opin ... -65074/amp

[D.ap]

https://www.cureasps.org/forum/viewtopi ... Gut#p12489