Immunotherapy is no longer a novelty, it has revolutionized the treatment of various cancers, transforming them into chronic diseases. An extraordinary result that is not for everyone, however. Some patients do not always respond effectively to treatment. For this reason, the world of research is at work in an attempt to decipher the reasons for this lack of response. Although there are many reasons, one of the main factors that can influence the effectiveness of immunotherapy is the microbiome, the set of microorganisms that populate our digestive tract. This is why changing its composition could be a useful strategy to improve the effect of anti-cancer treatments. In this regard, there are several studies presented at ASCO, the congress of the American Society of Clinical Oncology underway in Chicago, which go precisely in this direction: to modify the bacterial composition to improve the response to immunotherapy.
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by Tina Simoniello
The role of immunotherapy
Unlike the different cancer treatment strategies represented by surgery, chemo and molecular target therapies, immunotherapy consists in driving our immune system to always remain “on” to recognize and eliminate cancer cells. However, the effectiveness with which this occurs depends not only on the characteristics of the tumor and its micro-environment but also on the bacterial composition of the intestine. From the first years of clinical trials of immunotherapy it immediately became clear that antibiotic-based treatments, therefore capable of modifying the microbiome, negatively influenced the response to anti-cancer treatments. Starting from this observation, several studies have been born over the years that have shown how the presence or absence of some particular microorganisms had a correlation with a better or worse response.
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When the microbiome determines the answer
For example, last February an important study published in Nature Medicine concerning lung cancer showed that the presence of the microorganism Akkermansia muciniphila (Akk) is linked to the success of therapies. In particular, in patients who received immunotherapy as first-line treatment, 12-month survival was 59% in the Akk-positive group compared to 35% in the group of patients in which the organism was not present. According to this result, the latest in a long series, the analysis of the microbiota could really represent a predictive criterion in the treatment with immunotherapy.
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From stool transplantation to selective administration
The real goal of the research, however, is not only to predict the effects of therapies. Precisely because the microbiome is modifiable, piloting its composition could be a useful strategy to improve the effect of immunotherapy. To do this, the “stool transplant” has already been under study for some time. Preliminary results of an analysis conducted by researchers from the Lawson Health Research Institute were presented at the ASCO congress. The study, which involved patients with metastatic melanoma, involved the administration of some capsules containing fecal microorganisms from healthy donors before immunotherapy treatment. By analyzing the different actors of the immune response, scientists have shown that through this approach it is possible to restore the activity of some particular immune cells responsible for the good response against the tumor. An important result that demonstrates how through the transplant it is possible to act by improving therapies.
However, transplantation is not the only way. In recent times, instead of stool transplantation, the scientific community is looking with increasing interest at the identification and subsequent administration of only bacterial strains that can actually drive the immune response. Using a complex system of analysis of the composition of the microbiome, researchers at the biotech Immunobiome at ASCO identified in the microorganism Lactobacillus plantarumIMB19 (Lp IMB19) another potential ally in improving the response to immunotherapy. In animal models, they showed that the administration of a concentrate of Lp IMB19 in combination with an immunotherapy induced a significantly greater immune response than that obtained with immunotherapy alone.
But why does the bacterial composition influence therapies so importantly? The metabolites produced by microorganisms, substances capable of positively modulating the immune system, appear to be at the basis of the close link between bacteria and the functioning of immunotherapy. Being able to identify and modify the bacterial flora at will could be the right strategy to improve the efficiency of immunotherapy treatments.
The first human experiments
While waiting to identify new factors at play, we are beginning to move from animal model experiments to clinical trials. ASCO was informed that the BMC128 product developed by the Israeli biotech Biomica – the result of a mix of 4 different bacterial strains that in pre-clinical studies have proved useful in cases of melanoma – has started to be administered in a clinical trial of human phase I in combination with nivolumab in patients with melanoma or lung cancer. The results will be available in the coming months.
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