Immunomodulatory Effects of IL-2 and IL-15; Implications for Cancer Immunotherapy

Abstract

The type I cytokine family members interleukin-2 (IL-2) and IL-15 play important roles in the homeostasis of innate and adaptive immunity. Although IL-2 and IL-15 receptor complexes activate similar signal transduction cascades, triggering of these receptors results in different functional activities in lymphocytes. While IL-2 expands regulatory T cells and CD4+ helper T cells, IL-15 supports the development of central memory T cells and NK cells. Recent data have provided evidence that IL-2 and IL-15 differ in their ability to activate T and NK cells to resist various forms of immune suppression. The diverse roles of these two cytokines have on immune cells lead to critical therapeutic implications for cancer treatment. In this review, we discuss the distinct roles of IL-2 and IL-15 in activating various functions in T and NK cells with a particular focus on the signals that participate in the resistance of tumor-derived immune suppressive factors. Furthermore, we summarize current clinical applications of IL-2 and IL-15 in metastatic malignancies, either as monotherapy or in combination with other agents, and highlight the future trends for research on these cytokine-based immunotherapies.

Polysaccharide-based nanomedicines for cancer immunotherapy: A review

“…Cytokine therapy utilizes the immunomodulatory function of cytokines. Cytokines, such as interferons (IFNs) and interleukins (ILs, especially IL-2, IL-6, IL-12 and IL-15), are reported to be closely associated with antitumor immune responses, thus by administrating these cytokines externally, an enhanced antitumor activity could be achieved [ [87] , [88] , [89] , [90] , [91] ]. Currently, FDA-approved cytokines for cancer immunotherapy include IFN-α [ 92 ] and IL-2 [ 93 ].…”

Implication of Interleukin Family in Cancer Pathogenesis and Treatment

“…The next interleukins we consider are IL-2 and IL-15. Lundqvist et al [ 3 ] discuss the distinct roles of both interleukins in activating certain functions of immune cells, with a particular approach on the signals implicated in the resistance of immune suppressive factors related to the tumor microenvironment. The review summarizes modifications of these cytokines to amplify their antitumor efficacy while minimizing toxicity and the clinical applications in metastatic cancer.…”

iPSC-Derived Natural Killer Cells for Cancer Immunotherapy

“…Partly because it was the first cytokine to have its receptor cloned, IL-2 has long been used in several expansion protocols. However, IL-15 is now preferred, because unlike IL-2, it activates NK cells with high specificity, whereas IL-2 activates an assortment of immune cells, including regulatory T cells, which can suppress the anti-cancer response ( Yang and Lundqvist, 2020 ). Still, the optimal timing and dose of IL-15 need confirmation, as otherwise the expanded NK cells risk developing the exhausted phenotype ( Felices et al, 2018 ).…”