Details

Autor(en) / Beteiligte

• Su, Ee W
• Moore, Caitlin J
• Suriano, Samantha
• Johnson, Christopher Bryce
• Songalia, Neizel
• Patterson, Alicia
• Neitzke, Daniel J
• Andrijauskaite, Kristina
• Garrett-Mayer, Elizabeth
• Mehrotra, Shikhar
• Paulos, Chrystal M
• Doedens, Andrew L
• Goldrath, Ananda W
• Li, Zihai
• Cole, David J
• Rubinstein, Mark P

Titel

IL-2Rα mediates temporal regulation of IL-2 signaling and enhances immunotherapy

Ist Teil von

• Science translational medicine, 2015-10, Vol.7 (311), p.311ra170

Ort / Verlag

United States

Erscheinungsjahr

2015

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Interleukin-2 (IL-2) is a lymphocyte growth factor that is an important component of many immune-based cancer therapies. The efficacy of IL-2 is thought to be limited by the expansion of T regulatory cells, which express the high-affinity IL-2 receptor subunit IL-2Rα. IL-15 is under investigation as an alternative to IL-2. Although both cytokines signal through IL-2Rβγ, IL-15 does not bind IL-2Rα and therefore induces less T regulatory cell expansion. However, we found that transferred effector CD8(+) T cells induced curative responses in lymphoreplete mice only with IL-2-based therapy. Although conventional in vitro assays showed similar effector T cell responsiveness to IL-2 and IL-15, upon removal of free cytokine, IL-2 mediated sustained signaling dependent on IL-2Rα. Mechanistically, IL-2Rα sustained signaling by promoting a cell surface IL-2 reservoir and recycling of IL-2 back to the cell surface. Our results demonstrate that IL-2Rα endows T cells with the ability to compete temporally for limited IL-2 via mechanisms beyond ligand affinity. These results suggest that strategies to enhance IL-2Rα expression on tumor-reactive lymphocytes may facilitate the development of more effective IL-2-based therapies.