The association between adverse events and outcome under checkpoint inhibitors: Where is the deal?

•A review which lays out different potential contributions which can help to understand the IRAEs-outcome link.•There is a possibility to compute a multifactorial index to characterise patients as ICI sensitive or ICI unsensitive.•Prospective trails with ICIs are now fesaible to shape patient care beyond high -dose steroids. Recent reports have put into evidence the possibility of a link between immune-related adverse events (IRAEs) and treatment outcome, patients drawing a benefit from treatment being also exposed to the risk to develop toxicity. A still unanswered question remains the biological origin(s) which can sustain and explain such a relationship. The purpose of this review paper is to lay out different potential contributions which can help to understand the IRAEs-outcome link and to propose clinical perspectives taking advantage of this association. In this respect, pharmacokinetics aspects, immunological and immunogenetics implications have been taken into consideration. [Display omitted]