Immune Checkpoint Inhibitors (ICIs) are improving the survival of cancer patients, however only the 20-30% of treated patients present clinical benefits .Toxicity represents the major cause of reduced dosage, delayed drug administration and therapy discontinuation. Hence in the context of multiple treatment possibilities, the identification of predictive markers of response and toxicity is a challenging approach for drug selection in order to obtain the best clinical benefit while minimizing the side effects. Although the immune related side effects have become manageable to some extent by the use of corticosteroid therapy, new predictive indicators of response and toxicity are necessary to improve the management and the compliance to immunotherapy. The changes occurring in the microbiota composition has been proposed as one of the possible mechanism potentially explaining the pathogenesis of immune related toxicity.
The objective of this research project is to identify association between microbiome profile, toxicity and response to ICI treatment in patients affected by non small cell lung cancer (NSCLC).
The main challenge today for the clinics is to fully utilize the potential of ICI treatment in order to treat and cure the majority of patients, to limit the immune related events and toxicity and to better understand the dinamics of response to treatment. Is is conceivable that in a very short time ICI treatment will be proposed for all tumors and in early setting in the different protocols. We hypothesized that patients could be selected as responders or prone to high toxicity outcome on the basis of the nutritional status, microbioma profile and immune repertoire. The possibility of intervention is attractive. Diet, use of probiotics, prebiotics and antibiotics or stool transfer that can change microbiota profile, drugs that can modulate mucosal permeability and homeostasis as well as pretreatment immunotherapy/chemotherapy to increase the specific anti tumor T cell compartment are some of the strategies. We are today dealing with oncology treatments that have moved the attention from the tumor to the patients immune system and the multiple intersecting immunity regulatory networks. The further understanding of these mechanisms and the relation with clinical outcome will be the key for the development of protocols and guidelines for ICI treatment with maximized curative potential.