Research

FMT emerging as a booster shot to immunotherapy-resistant cancer


Immunotherapy may have revolutionised the treatment of many cancers including melanoma, but it might be the gut microbiota that helps further advance those gains.

Two phase 1 trials published earlier this year suggest that restoring the gut microbiome via faecal microbiota transplantation (FMT) can help restore sensitivity to anti–PD-1 immunotherapy in patients whose metastatic melanoma has persisted or progressed during treatment.

A US study, published in Science, showed FMT derived from melanoma patients who were responders to anti–PD-1 immunotherapy was well tolerated, induced taxa changes and provided clinical benefit in 6 of 15 patients with PD-1-refractory melanoma.

An Israeli study, also published in Science, also found FMT induced clinical responses in three of 10 patients with PD-1-refractory melanoma after re-induction with anti–PD-1 immunotherapy.

Treatment with FMT was associated with favorable changes in immune cell infiltrates and gene expression profiles in both the gut lamina propria and the tumor microenvironment.

The studies suggested that altering the mix of bacteria in the gut microbiome can enhance the efficacy of immunotherapy in a subset of patients.

Ms Rebecca Simpson, a PhD Candidate at the Melanoma Institute Australia and Charles Perkins Centre at the University of Sydney, told the limbic that primary and acquired resistance to immunotherapy remain key challenges in the management of patients with advanced melanoma.

“The microbiome is an important factor which underpins immune function, it is therefore relevant to both anti-tumour responses and the development of inflammatory toxicities which frequently accompany treatment.”

“The promising aspect of the microbiome is that it is also modifiable, establishing the microbiome as a particularly attractive target to overcome therapeutic resistance. What is the ideal microbiome to promote immunotherapy response and how to best target the microbiome to overcome resistance are therefore areas of high interest,” she said.

She said research was underway at Melanoma Institute Australia’s Translational Research Laboratory aiming to modulate the microbiome to induce an immune and microbiome landscape which was more conducive to respond to immunotherapies.

“These days, given the abundant evidence highlighting the role of the gut microbiome in modulating immune function and more recently in the context of cancer immunotherapy, there is a growing appreciation of the potential application of FMT in this context or other microbiome modulating interventions.”

“Although such applications are in their very early days and trials in Australian melanoma patients receiving immunotherapy are currently not established.”

 

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