ArticleFrontiers in immunology2026
IL-7Rα signaling potentiates the anti-tumor activity of NK92 cells.
Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Natural killer (NK) cells are promising candidates for cancer immunotherapy due to their safety and potent anti-tumor activity. However, their therapeutic efficacy is often limited by poor persistence and activity within the tumor microenvironment (TME) caused by a lack of essential cytokines. Methods: To overcome cytokine dependence, we engineered NK92, primary NK (pNK), and chimeric antigen receptor (CAR)-NK92 cells to express an interleukin-7 receptor with an insertion mutation (IL-7R-IM), which induces constitutive signaling. We evaluated the proliferation, viability, and cytotoxicity of these cells Results: NK92-IL-7R-IM cells exhibited sustained proliferation and high viability independent of exogenous cytokines, superior to IL-2-activated NK cells. This enhanced functionality was driven by the constitutive activation of the JAK/STAT, AKT, and ERK signaling pathways, leading to the upregulation of cytotoxicity-related genes ( Conclusions: The expression of IL-7R-IM confers cytokine independence and robust anti-tumor activity to NK and CAR-NK cells. This strategy offers a practical solution to improve the persistence and efficacy of off-the-shelf NK cell therapeutics for clinical application.
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