IL-2 is inactivated by the acidic pH environment of tumors enabling engineering of a pH-selective mutein

• DOI: 10.1126/sciimmunol.ade5686
• Publication Date: 2022-12-02T18:58:11Z
• Authors: Silvia Gaggero; Jonathan Martinez...; Adeline Cozzani; Paul K. Fyfe; Malo Leprohon; Jie Yang; F. Emil Thomasen; Hauke Winkelmann; Romain Magnez; Alberto G. Conti; Stephan Wilmes; Elizabeth Pohler; Manuel van Gijsel...; Xavier Thuru; Bruno Quesnel; Fabrice Soncin; Jacob Piehler; Kresten Lindorff-...; Rahul Roychoudhuri; Ignacio Moraga; Suman Mitra
• Keywords: STAT5

Cytokines interact with their receptors in the extracellular space to control immune responses. How physicochemical properties of influence cytokine signaling is incompletely elucidated. Here, we show that activity interleukin-2 (IL-2), a critical T cell immunity, profoundly affected by pH, limiting IL-2 within acidic environment tumors. Generation lactic acid tumors limits STAT5 activation, effector differentiation, and antitumor immunity CD8