Successful Immunotherapy may be the result of one bacterium

Successful Immunotherapy may be the result of one bacterium

Research suggests that Akkermansia muciniphila maybe responsible for the success of PD-1 immunotherapy drugs with melanoma, NSCLC and renal cell carcinoma.

In 2018, a study (1) showed that gut bacteria could influence the success of PD-1 Immunotherapy, or so called 'Immune Checkpoint Inhibitor' drugs. Cancer immunotherapy was touted as the big breakthrough in cancer, but the drugs didn’t work as well as expected. Since they aimed to ‘unblock’ T-cells making these more able to attack the cancer, one hypothesis was that somehow, most patients simply did not have enough T-cells.

The study by Routy et al. indicated that a non-host factor, especially one particular host gut microbe, significantly influenced patient response to Immune Checkpoint Inhibitor (ICI) immunotherapy. The researchers also found that the use of antibiotics during ICI immunotherapy reduced response to the treatment. 

Chris Woollams, former Oxford University biochemist and a founder of CANCERactive said, “We have made this point consistently. We have noted that high fibre diets improve immunotherapy effectiveness, certain probiotics also, as does vitamin D. All these will put levels of T-cells up and/or make them more effective. Equally, using antibiotics at the same time, or conventional chemo, or even not giving the gut microbiome time to recover after these damaging drugs, can all significantly reduce the effectiveness of Immunotherapy drugs like Nivolumab and Keytruda.

In previous mice studies, the same researchers had shown that giving antibiotics with the immunotherapy actually increased tumour size and decreased survival in melanoma and sarcoma cancers. Immunotherapy relies on the integrity of the microbiome (2) a fact that should be noted when Oncologists want to switch a patient straight from chemotherapy drugs onto Immunotherapy.

Just in case you were thinking that mice are not humans, the researchers then analysed data from Humans – in 249 patients with NSCLC, renal carcinoma or urothelial cancer, 69 patients received antibiotics before or during the immunotherapy treatment and had significantly shorter time before disease progression and had subsequent lowered survival. However, other drugs and Proton Pum Inhibitors, which are notoriously bad for the microbiome, did not have this survival-damaging effect.

So the researchers then hypothesised that it was not the overall microbiome damage, but more the loss of specific strains of gut bacteria. Using metagenomics, they identified (4) one bacterium as crucial to the success of immunotherapy with NSCLC and renal carcinoma - Akkermansia municiphila. This bacterium is important in lining the gut with mucous (mucin) and preventing leaky gut. Leaky gut brings compounds from the gut directly into the bloodstream, and prompts an inflammatory response.

However, this is not always the case. In Melanoma patients, it appears that the diversity of the microbiome is more important in delivering more effective PD-1 immunotherapy response (5). It's not about one bacterium but the totality.

Chris Woollams adds, “Like most commensal bacteria, A. muciniphilia loves soluble fibre like oats, nuts and seeds, vegetables and pulse, and particularly polyphenols like those in cranberry, pomegranate and EGCG in green tea. These polyphenols help it produce mucin. It's the third layer in the gut; you have the wall, the lining and the mucin layer."

Go to: Polyphenols – top foods for health

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References

  1. Routy B, Le Chatelier E, Derosa L, et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science 2018;359:91–7. 
  2. Anticancer immunotherapy relies on gut microbiota; Science; 2015 Nov 27;350(6264):1079-84.
  3. Sivan A, Corrales L, Hubert N, et al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science 2015;350:1084–9
  4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6233902/
  5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6482659/

 


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2021 Research
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