By some estimates, over 60% of the body’s immune cells ‘live’ in the gut. So much so that the scientific community has wondered: can the dishes we bring to the table influence the body’s response to anti-tumor treatments, including immunotherapy? The evidence that seems to suggest this has recently become more and more numerous. Apples, pears, plums and kiwis; but also walnuts, pistachios and peanuts. And beans, chickpeas, lentils, carrots, aubergines, artichokes, cereals and even dark chocolate: they are all foods rich in fiber capable of ‘nourishing’ the microbiome – the set of microorganisms housed in the intestine – and consequently, they hypothesize experts, can increase the effectiveness of immunotherapy.
There are several ongoing studies around the world that aim to show a link between a high-fiber diet and greater effectiveness of immunotherapy. And within the next year a new clinical trial is planned at the Irccs San Raffaele hospital in Milan which involves the administration of a controlled diet rich in fiber in patients with indolent myeloma. The latest innovations in tumor immunotherapy and how this can be modulated by the intestinal microbiome will be discussed in Milan during Cicon23, the International Cancer Immunotherapy Conference which attracted over a thousand scientists from more than 38 countries. The event, which will continue until Saturday 23 September, is organized by international scientific societies together with the Italian Network for Tumor Biotherapy (Nibit).
Among the ongoing research, experts report, there are studies on fecal transplants and work that aims to confirm the effects that fatty acids have on the immune response against tumors. “Immunotherapy has revolutionized the treatment of many tumors – explains Pier Francesco Ferrucci, director of the Tumor Biotherapy Unit at the European Institute of Oncology (IEO) and president of Nibit – However, not all patients respond in the same way. Hence the hypothesis, which has now become a certainty, that the composition of a patient’s intestinal microbiome influences the success of immunotherapy treatment. In essence, patients who host certain intestinal bacteria seem to respond better to immunotherapy than patients who do not they are deprived.” Moreover, points out Antonio Sica, secretary of Nibit, director of General Pathology at the University of Eastern Piedmont and of the Laboratory of Molecular Pathology and Immunology at Irccs Humanitas in Rozzano (Milan), “if we do the numerical calculation of our cells and of the bacteria that live with us there are 10 times more of them and this symbiosis conditions the homeostasis of the tissues and also the metabolism”.
“Today – explains Sica – there is a great deal of attention, for example, on the component of the microbiota that colonizes the mucous membranes, the interface between our organism and the environment and the first defense barrier. And there is attention on the impact of dysbiosis”, alterations of the bacterial flora “which are also associated with the progression of the disease. In this regard there is a lot of interest in nutritional approaches that can allow it to be restored”.
Among the hypotheses considered interesting by experts is the one, based on recent scientific evidence, according to which giving patients a diet rich in fiber could increase the probability that cancer treatment will be more effective. “We have known for some time that the microbiome is a crucial part of our immune system – specifies Vincenzo Bronte, scientific director of the Veneto Oncology Institute and next-president of Nibit – But only recently have we accumulated sufficient evidence according to which these microbes can be ‘modified’ to positively influence the outcome of cancer treatments, including immunotherapy.”
Some research groups are trying to overcome resistance to immunotherapy by carrying out fecal transplants: ‘good’ intestinal microbes are taken from stool samples of patients who have responded well to the drugs and then transplanted via colonoscopy to another patient. Another path is to design ad hoc diets capable of modifying the microbiota to make it an ‘ally’ of immunotherapy. “In this regard, we are planning a clinical trial on patients suffering from indolent myeloma – states Matteo Bellone, head of the Cellular Immunology Unit of the San Raffaele in Milan, one of the organizers of Cicon23 – We will propose to patients a controlled diet rich in fiber with l The aim is to understand its effects, not only on the composition of the intestinal microbiome, but also on the metabolic modifications of the organism, and on the course and prognosis of the disease”.
The Milan event will also be an opportunity to talk about immunometabolism. “It is known that all cells require energy to carry out their vital functions and that this capacity is under the control of metabolic pathways – recalls Sica – In this scenario, recent evidence has demonstrated that tumors engage in metabolic competition with cells immune systems, depriving them of essential nutrients for energy production and thus establishing a condition of immunosuppression which favors tumor growth and the onset of mechanisms of resistance to therapies”. New studies therefore aim to understand the mechanisms that govern patients’ immunometabolism in order to restore effective immune responses. In this context, in a work published in ‘Cell Metabolism’, which will be illustrated by Teresa Manzo of IEO, the powerful effects that fatty acids exert on the immune response against tumors are demonstrated.
But cholesterol is also involved. “Recent studies demonstrate how the altered metabolism of cholesterol and lipids is able to influence the functionality of immune cells – reports Vincenzo Russo, associate professor of General Pathology at the Faculty of Medicine of the Vita-Salute San Raffaele University of Milan, among the organizers of Cicon3 – With Paolo Ascierto, chief oncologist of the National Cancer Institute of Naples, we will present clinical results on the greater effectiveness of immunotherapy in combination with treatments blocking cholesterol synthesis”.
Arlene Sharpe, a scientist at Harvard University, will also take part in Cicon23, studying the mechanisms that allow the intestinal microbiota to influence the immune response to immune checkpoints. “An entire session will be dedicated to how nutrition can affect the immune system and the patient’s ability to respond, not only to immunotherapy, but also to more traditional treatments such as chemo,” concludes Bellone. But “it is important that nutrition and the use of probiotics are suggested by experts not only in nutrition but also in the disease in question. Unfortunately, we have witnessed a worsening of the disease when patients did not seek expert advice. Therefore, yes to personalized nutrition, but under the supervision of your trusted oncologist”.
