Introduction

IL-1 plays an important role in both innate and adaptive immune responses. IL-1R8/TIR8/SIGIRR is a receptor acting as negative regulator of inflammatory and adaptive responses mediated by ligands of the IL-1 system. Natural killer (NK) cells are involved in the resistance against pathogens and are implicated in the regulation of adaptive immune responses against cancer. NK cell-based therapies miss their beneficial effects following the NK cell maturation impairment. A strategy to allow NK cell maturation can ensure NK cells features restore.

Technical features

We found that IL-1R8 is expressed in murine and human NK cells and that is involved in NK maturation, antitumor and antiviral activity (Fig. 1). We observed that in preclinical models of liver and lung metastasis of mice, IL-1R8-deficent NK cells significantly and dramatically reduce the number and volume of metastasis (Fig. 2). Moreover, we observed that IL-1R8 expression level inversely correlates with NK cell activation in humans and that IL-1R8 genetic inactivation through siRNA in human NK cells is associated with enhanced NK cell activation, in terms of IFNy production and CD69 expression, indicating that IL-1R8 determines a negative role of NK cell activation and that its inactivation unleashes human NK cell effector function (Fig.3). Given that IL-1R8 genetic inactivation in NK cells could have a beneficial effect in NK cell-based cell therapies, the object of the invention is a human NK or T cell stably or transiently deficient in the expression and/or activity or IL1R8.

Possible Applications

• Useful in several NK cells- based therapies e.g. for treatment and/or prevention of cancer, metastasis or microbial/viral infections.

Advantages

• The method can be applied for tumor diagnosis.