Targeting PI3Kδ One man’s meat is another man’s poison

In our recent article, “PI3Kδ is essential for tumor clearance mediated by cytotoxic T lymphocytes,”1 we set an example for the preclinical evaluation of anticancer drugs, considering both pharmacologi-cal and immunological aspects. We used the power of murine models to study the immunological consequences of the abla-tion or pharmacological blockage of phos-phoinositide-3-kinase δ (PI3Kδ). Our findings can be viewed as a contribution to translational research, as these insights are valuable to anticipate issues that may otherwise be evident only at late stages of clinical development. PI3Ks constitute central hubs in cellu-lar signaling networks. The main compo-nents of the module, namely PI3K, AKT and mTOR, are crucial to support cell sur-vival, adaptation of cell growth to exter-nal stimuli and nutrient supply, as well as to suppress apoptosis.2 Class I PI3Ks are heterodimeric molecules compris-ing a catalytic and a regulatory subunit. There are four catalytic isoforms of Class I PI3Ks (Class IA p110α, p110β, p110δ and Class IB p110γ). The expression of PI3K