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Science Immunology

  • Volume 7
  • Issue 78
  • Dec 2022
Go to Science Immunology
Go to Science Immunology

ONLINE COVER IL-2 Mutein Passes an Acid Test. This month’s cover depicts a glycolytic tumor releasing lactic acid molecules, establishing an acidic tumor microenvironment (TME). The low pH of the TME suppresses antitumor immune responses and favors tumor growth. Gaggero and Martinez-Fabregas et al. report that cytokines are extremely sensitive to the acidic pH found in tumors and lymph nodes. The activity of IL-2, a cytokine central to T cell responses, is highly limited at acidic pH. Using in vitro evolution, they identify a new IL-2 variant, Switch-2, that exhibits enhanced activity at acidic pH but, surprisingly, exhibits reduced activity at the neutral pH found in healthy tissue. Switch-2 therapy in mice triggered potent antitumor responses while avoiding the severe systemic toxicity associated with current high-dose IL-2 therapies.

Credit: Paul K. Fyfe

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Science Immunology publishes original, peer-reviewed, science-based research articles that report critical advances in all areas of immunological research, including important new tools and techniques.

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