Research projects

Targeting the gut microbiome to make immunotherapies more effective

Researcher

Dr Luigi Nezi

Project period

May 2022 - April 2025

Country

Research Institute

European Institute of Oncology (IEO)

Cancer types

Bowel cancer

Award amount

£185,900

Project aim

Dr Luigi Nezi and his team are studying how microbes and what they produce in the gut, also known as the gut microbiome, influence the ability of the immune system to fight cancer. They hope that this could be exploited to make the immune system stronger and more responsive to immunotherapy against bowel cancer.

Hope for the future

Bowel cancer is one of the most common types of cancer worldwide, but it is often diagnosed once the cancer has already spread and is much harder to treat. Immunotherapies, a type of treatment that prompts the immune system to kill cancer cells, have the potential to cure, but do not work in many patients. Finding a way to make immunotherapies work for these patients would save many lives.

Dr Luigi Nezi and his team recently discovered that a build-up of specific fats in the tumour suppresses certain immune cells from working properly and this may impact on how well bowel cancer patients respond to immunotherapy. The researchers previously found that microbes in the gut contribute to this phenomenon. By studying these microbes more thoroughly in bowel cancer patients they hope to reveal new ways to make immunotherapies more effective.

Meet the scientist

Dr Luigi Nezi comes from a small village in the south of Italy, nested between golden wheat fields, century-old olive trees and the crystal-clear Adriatic Sea of Puglia. That’s why he loves any outdoor activity that takes me back in contact with nature. Luigi also plays basketball, football and is a fix-gear bicycle fanatic. “In the last 6 years, all my hobbies have converged on two points: my six-year old boy and five-year old girl!”

The science

Research has shown that the immune system plays a key role in how effective treatments are against bowel cancer and how quickly it progresses. Immunotherapies, such as immune checkpoint inhibitors (ICIs), can be highly effective for some patients with bowel tumours, but most patients do not respond, and there are currently no good ways of testing who is likely to benefit from this type of treatment.

Dr Nezi and his team recently discovered that T cells, a type of immune cells with anti-tumour function, were suppressed by a type of fats that build up also within bowel tumours. By analyzing the bacteria that were living there, the group of researchers concluded that the gut microbiome can contribute to those fats and help bowel tumours to grow faster by suppressing the T cells. They believe that this can be one of the reasons why most of the bowel tumours don’t respond to immunotherapy.

The researchers now hope to study the microbiome of bowel cancer patients in more detail, including how it interacts with different types of immune cells. They will also test whether targeting the microbiome could make ICIs more effective at treating bowel tumours.

I have a history of cancer in my family, past and present. But my personal connection with the disease cannot be defined only through that. The suffering of every patient I met while working in the cancer hospitals, and the complexity of the science behind cancer, are the real drivers of my everyday life in the lab.

Dr Luigi Nezi