Editors' ChoiceImmunology

Immunotherapy: Reduce, reuse, recycle

Sci. Signal.  03 Nov 2015:
Vol. 8, Issue 401, pp. ec324
DOI: 10.1126/scisignal.aad7794

Interleukin-2 (IL-2) is a cytokine used in the clinic to boost immune cell responses to cancer. The related cytokine IL-15 also stimulates the proliferation of effector T cells but, unlike IL-2, does not stimulate proliferation of regulatory T cells. Su et al. demonstrate that, although IL-15 may be effective in lymphopenic patients, IL-2 therapy may be needed in patients who retain immune cells, where T cells compete for available cytokine. In isolated T cells, addition of IL-2, but not IL-15, resulted in sustained signaling even after the cytokine was removed, because IL-2 remained bound to the high-affinity receptor subunit IL-2Rα, which does not bind IL-15. IL-2Rα forms a cell surface reservoir of IL-2 and also enabled recycling of IL-2 back to the cell surface, thereby increasing the efficiency of signaling by limited quantities of cytokine.

E. W. Su, C. J. Moore, S. Suriano, C. B. Johnson, N. Songalia, A. Patterson, D. J. Neitzke, K. Andrijauskaite, E. Garrett-Mayer, S. Mehrotra, C. M. Paulos, A. L. Doedens, A. W. Goldrath, Z. Li, D. J. Cole, M. P. Rubinstein, IL-2Rα mediates temporal regulation of IL-2 signaling and enhances immunotherapy. Sci. Transl. Med. 7, 311ra170 (2015). [Abstract]