Fecal therapy of melanoma

Stool transplantation helps melanoma patients to start responding to immunotherapy

Maria Tolmacheva, XX2 century

Changing the gut microbiome can help patients with advanced melanoma begin to respond to immunotherapy if it did not help them before. This discovery is especially important because melanoma immunotherapy fails in 40% of cases.

The results of the second phase of clinical trials of this technique were recently published in the journal Science (Davar et al., Fecal microbiota transplant overcomes resistance to anti–PD-1 therapy in melanoma patients). During the trials, researchers from the Hillman Cancer Center of the University of Pittsburgh (UPMC Hillman Cancer Center) and the National Cancer Institute of the USA (National Cancer Institute) prescribed fecal microbiota transplantation (TFM) and anti-PD-1 immunotherapy to melanoma patients who did not respond to other treatments, including immunotherapy.

– TFM is just a means to an end. We know that the composition of intestinal microorganisms – intestinal bacteria – can change the likelihood of a reaction to immunotherapy. But what kind of microorganisms are needed? After all, there are about 100 trillion intestinal bacteria in the human microbiome, says study author Diwakar Davar, an oncologist, associate professor of medicine at the University of Pittsburgh.

Stool transplantation covers a wide range of microbes, as trillions of bacteria enter the intestine with feces at once. Davar and his colleagues collected stool samples from patients who responded extremely well to anti-PD-1 immunotherapy and tested them for infectious pathogens before transplanting these samples to patients with advanced melanoma who had never previously responded to immunotherapy. Then the patients were given pembrolizumab, a drug against PD-1. And it worked.

Of the 15 patients with advanced melanoma who received combined treatment, including TFM and anti-PD-1-immunotherapy, six either had tumors reduced or diseases that lasted more than a year stabilized.

– The probability that the patients treated in this study spontaneously reacted to repeated anti-PD-1 immunotherapy is very small. Thus, any positive response should be associated with fecal transplantation, said study co-author, immunologist Hassan Zarour.

Davar and Zarur hope to conduct a larger trial involving melanoma patients, as well as to assess whether TFM can be effective in treating other cancers. Ultimately, their goal is to replace TFM with tablets containing a cocktail of the most beneficial microbes to enhance immunotherapy, but there are still several years of work before that.

– Even if much remains to be done, our study gives hope for microbiomic cancer therapy, says Zarur.

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