Immunotherapy has been a great addition to the treatment arsenal to fight cancer. Unfortunately, most of the patients do not benefit from immunotherapy. We are delighted that with support of this WCRF grant we will be able to investigate if we can induce a favorable change in the gut bacteria by fiber supplementation with the aim to improve responses to immunotherapy in patients with metastatic melanoma. We look forward to starting this project!
Asst Prof Kalijn Bol
Background
Immunotherapy is a new treatment strategy for cancer. Immunotherapy aims to activate the patient’s own immune system to kill cancer cells. In patients with metastatic melanoma, the most aggressive form of skin cancer, immunotherapy has shown to be of benefit for about half of the patients, inducing long-lasting cancer control and possibly even cure. Unfortunately, the other half of patients do not benefit from immunotherapy and survival is poor. Response to immunotherapy in patients with melanoma is related to the bacteria present in their gut. Bacteria that play an active role in the degradation of dietary fibres seem to have the strongest link with response to immunotherapy. Animal studies show that response to immunotherapy can be improved by increasing dietary fibre intake. However, this is yet to be validated in human.
Aims and objectives
The aim of this project is to induce a favourable change in the gut bacteria of patients with metastatic melanoma to improve the chance of benefit from immunotherapy.
To reach this aim the patient’s regular diet will be supplemented with extra fibres during standard-of-care immunotherapy. We will expect the fibres to 1) induce a favourable change in the gut bacteria, 2) the favourable gut bacteria to activate relevant immune cells, and 3) the active immune cells to kill the cancer cells.
How it will be done
We will perform a clinical study in which patients with metastatic melanoma scheduled to start with immunotherapy will receive either extra fibres to supplement their regular diet or a placebo. To analyze the effect of the extra fibres on the gut bacteria (1), we will measure the gut bacteria in patient stools. The effect on the activation of the immune cells (2) will be measured in patient blood. Lastly, the response to treatment (3), killing of the cancer cells, will be visualized by making scans to see if the tumor reduces in size or completely disappears.
Potential impact
This project could be the first step to prove that by changing the gut bacteria the response to immunotherapy can be improved in humans. The advantage of this approach is that the supplementation of the diet with extra fibres is safe, easy to use, and inexpensive. This could impact not only the lives of patients with melanoma, but also their families and patients with other cancer types treated with immunotherapy.