Effect of probiotic supplementation on immune system and microbiota composition in allergic patients with rhinitis and asthma: a pilot study & Biologic evaluation of new IDO1 inhibitors as possible hit compounds useful against immune escape in cancer therapy

Part I: Allergies has been on the rise and scientific evidence has shown that genetic predisposition and environmental factors influence the development of sensitization. In 1989 Strachan D.P. postulated the "Hygiene hypothesis", in his opinion, microbial infections could protect from atopic diseases. The identification of allergy protective bacteria and their relationship with human cells confirm the pivotal role of the microflora in development of the immune system. Lately, attention to health and prevention together with improvement of alternative medicine increase the use of food supplements like Probiotics. Probiotics, containing beneficial microorganisms, have a protective gastrointestinal effect, but even more, may modulate the immune system thanks to their influence on microbiota. Many researchers focused their attention on the use of probiotics in allergies. In fact, there are several studies demonstrating that the administration of probiotics could prevent the onset of allergic sensitizations and improve the symptoms of atopic dermatitis and allergic rhinitis. Unfortunately, data available are controversial and there is still a lot of work to be done to confirm the probiotic's usefulness on allergies. Part II: Tryptophan (Trp) is an important metabolic regulator of cancer progression. It was demonstrated that this amino acid has beneficial effects on intrinsic malignant properties of tumour cells as well as on anti-tumour immune responses. Three enzymes, Indoleamine 2,3 dioxygenase 1 and 2 (IDO1/2), and tryptophan-2,3-dioxygenase (TDO), are involved in Trp metabolism. ID01 is the most studied. It catalyses the first, rate-limiting step of the so-called "kynurenine (Kyn) pathway", which converts Trp into the immunosuppressive metabolite Kyn. Some tissues express constitutively IDO1, but the enzyme can also be induced in antigen presenting cells promoting immune tolerance to cancer antigens. Depletion of Trp and accumulation of Kyn are responsible of the immunomodulatory function of IDO1. Inhibiting IDO1 using small-molecules inhibitors give hopes in the field of immune-oncology. While high IDO1 levels may elude anticancer immunosurveillance. IDO1 inhibition could restore anti-tumour immune response and used in synergy with checkpoint inhibitors could be more effective against the progression of tumour. It is for these reasons that, recently, ID01 inhibitors represent promising therapeutic candidates in cancer.