SCIENCE: Fecal microbiota transplantation may help eliminate resistance to immunotherapy in patients with melanoma

Two phase 1 clinical studies have shown that in some patients with metastatic melanoma that persists or progresses during anti-programmed cell death protein 1 (anti- PD-1 ) drug treatment, fecal microbiota transplantation (FMT) may restore anti- PD- 1 Inhibition of sensitivity
.

Further research is needed to better identify microbial, circulating, and intratumoral biomarkers in order to select patients most likely to benefit from melanoma treatment based on the fecal microbiome

PD-1 PD-1

Recently published in SCIENCE magazine reported that the two articles, FMT may contribute to intestinal microflora in patients with advanced melanoma were reprogrammed, which could neutralize against PD-1 immune therapy drug resistance
.

FMT may help to reprogram the gut microbiota of patients with advanced melanoma, which may neutralize and fight FMT may help reprogram the gut microbiota of patients with advanced melanoma, which may neutralize and fight PD- 1 Immunotherapy resistance
.

PD-1 immunotherapy resistance

Some observational studies have shown a correlation between the gut microbiota of patients with metastatic melanoma and their response to immune checkpoint inhibitor (CPI) treatment
.

While in preclinical mouse models of intestinal microbiota can affect tumor against PD-1 response immunotherapy, but not in the anti- PD-1 were FMT clinical trials ongoing or progression of human melanoma patients after immunotherapy Research

PD-1 PD-1

One of the studies included 7 FMT donors and 15 recipients from the University of Pittsburgh Hillman Medical Center (UPMC) Department of Medicine in Pittsburgh, Pennsylvania, and the National Institutes of Health Clinical Center in Bethesda, Maryland
.

The second trial included 2 FMT donors and 10 recipients from the Ella Lemelbaum Immuno-Oncology Institute of Tel-HaShomer Sheba Medical Center in Israel

PD-1

The FMT protocol in both studies included the initial consumption of the native microbial community, which included vancomycin and neomycin
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The patient then undergoes colonoscopy FMT and oral stool capsules, and then again induces nivolumab anti- PD-1 therapy (in the Israeli study), or only through colonoscopy FMT, followed by pembrolizumab (in the Pittsburgh study) )

PD-1

The results of the 15 FMT recipients in the Pittsburgh study included 3 PR patients and 3 stable patients
.

The 10 FMT recipients in the Israeli study also found similar results: 1 CR and 2 PRs

FMT is safe, and changing the bacterial combination in the intestinal microbiota can improve the efficacy of immunotherapy in some patients

This study proves that the tumor microenvironment can be reprogrammed to manipulate the microbiome to enhance and improve the immunotherapy effect of advanced melanoma, and to overcome resistance.

Tumor immunity PD-1 PD-1

In the Israeli study, researchers observed the clinical response of 3 patients, including 2 PRs and 1 CR
.

In addition to observing the clinical anti-tumor response, the two teams conducted extensive molecular testing to support the hypothesis that FMT changes the gut microbiome of some patients, which affects the composition of their gut-related immune cells and tumor infiltrating immune cells

FMT therapy is associated with immune cell infiltration and gene expression profile changes in the intestinal lamina propria and tumor microenvironment FMT therapy is associated with immune cell infiltration and gene expression profile changes in the intestinal lamina propria and tumor microenvironment

According to these two studies, FMT may have a therapeutic effect on patients treated with CPI
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However, for this therapy to be approved, some clinical, regulatory, and scientific issues need to be resolved
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In addition, a larger-scale study is needed in a clear post-CPI population to prove the effectiveness of FMT
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At present, due to the complexity of microbiota regulation and related risks caused by improper operation, microbiota regulation should continue to be carried out in the highly monitored environment of clinical trials
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These two studies only provide a proof of principle, and the data cannot be exaggerated, because only 6 out of 15 patients have good results
.
Further research is needed to better identify microbes, circulation, and intratumoral biomarkers in order to select patients who are most likely to benefit from microbiome-based melanoma treatment
.
Future work requires a better understanding of the source of donor FMT, transplantation procedures, and recipient phenotypes that are the response characteristics required for successful CPI-FMT combination therapy
.

Original source

1.
Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients.
BY EREZ N.
BARUCH, SCIENCE05 FEB 2021: 602-609.
 

Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients.
BY EREZ N.
BARUCH, SCIENCE05 FEB 2021: 602-609.
 

2.
Fecal microbiota transplant overcomes resistance to anti–PD-1 therapy in melanoma patients.
BY DIWAKAR DAVAR, SCIENCE05 FEB 2021: 595-602

Fecal microbiota transplant overcomes resistance to anti- PD-1 therapy in melanoma patients BY DIWAKAR DAVAR, SCIENCE05 FEB 2021:.
595-602 in this message