Type I interferons (IFNs) activate intracellular antimicrobial programmes and influence the development of innate and adaptive immune responses. We will discuss our results by addressing the biology of IFN in Down syndrome (DS). This syndrome is the consequence of a chromosomal anomaly known as "trisomy 21" in which chromosome 21 is partially or totally tripled. The subunits that make up the IFN-I receptor (IFNAR1 and IFNAR2), like other genes of immunological relevance, are encoded on this chromosome and their expression is severely increased. This generates an important immunological dysregulation. We will discuss the features of the T cell compartment, Tregs functionality, and the impact of IFN signalling on the different T cell subsets, that could explain the different susceptibilities of this population to develop some pathologies such as solid tumors and autoimmunity. On the other hand, competent type I IFN signalling underlies most anti-tumor immune mechanisms and has recently proven critical to the efficacy of several anticancer agents and immunotherapy.  In this talk, we will discuss our recent findings regarding the potential of TLR agonists as type I-IFN inducers and consequently, as strong modulators of the tumor infiltrate composition, capable of switching the immune suppressive tumor environment to anti-tumor immunity.