PI3Kδ Inhibitors as Immunomodulatory Agents for the Treatment of Lymphoma Patients

SIMPLE SUMMARY: This review focuses on the effects that a class of drugs, PI3Kδ inhibitors, used for the treatment of patients with lymphoma can have not on the neoplastic cells but on the normal cells and how this effect can modulate the immune response and potentially contribute to the anti-tumor response. ABSTRACT: The development of small molecules able to block specific or multiple isoforms of phosphoinositide 3-kinases (PI3K) has already been an active field of research for many years in the cancer field. PI3Kδ inhibitors are among the targeted agents most extensively studied for the treatment of lymphoma patients and PI3Kδ inhibitors are already approved by regulatory agencies. More recently, it became clear that the anti-tumor activity of PI3K inhibitors might not be due only to a direct effect on the cancer cells but it can also be mediated via inhibition of the kinases in non-neoplastic cells present in the tumor microenvironment. T-cells represent an important component of the tumor microenvironment and they comprise different subpopulations that can have both anti- and pro-tumor effects. In this review article, we discuss the effects that PI3Kδ inhibitors exert on the immune system with a particular focus on the T-cell compartment.