Interleukin-15 receptor complex (IL-15R)

The Interleukin-15 receptor complex, specifically in the context of membrane-bound interleukin-15 (mbIL-15) on tumor-infiltrating lymphocytes (TILs), is a critical signaling assembly in adoptive cell therapy. Naturally, IL-15 signaling involves the trans-presentation of the cytokine by the IL-15 receptor alpha (IL-15RA) subunit to a heterodimeric receptor composed of the IL-15 receptor beta (CD122) and common gamma (CD132) chains (UniProt P40933, P14784). In engineered TILs, a membrane-tethered fusion of IL-15 and IL-15RA is expressed to facilitate autonomous cis signaling through the CD122/CD132 complex (PubMed 31515460). This interaction activates the JAK/STAT5 pathway, which is vital for the survival, proliferation, and metabolic fitness of CD8+ T cells and NK cells within the immunosuppressive tumor microenvironment (PubMed 27160754). By providing a cell-intrinsic survival signal, mbIL-15 reduces the requirement for systemic IL-2 administration, thereby minimizing associated toxicities such as vascular leak syndrome. This engineered complex is currently being evaluated in clinical trials to improve the persistence and anti-tumor efficacy of TIL therapies in solid malignancies (Obsidian Therapeutics, 2023).

Other names

Membrane-bound interleukin-15mbIL-15IL-15/IL-15RA complexCD122/CD132 complexMembrane-bound interleukin-15 receptor complex

Activation of the JAK/STAT signaling pathway through the IL-15 receptor beta (CD122) and gamma (CD132) subunits via a membrane-tethered IL-15/IL-15RA fusion protein.