IKKα-deficient lung adenocarcinomas generate an immunosuppressive microenvironment by overproducing Treg-inducing cytokines
Na‐Young Song, Xin Li, Buyong Ma, Jami Willette‐Brown, Feng Zhu, Chengfei Jiang, Ling Su, Jyoti Shetty, Yongmei Zhao, Gongping Shi, Sayantan Banerjee, Xiaolin Wu, Bao Tran, Ruth Nussinov, Michael Karin, Yinling Hu
Abstract
Significance This study reveals that impaired IKKα expression or activity in lung cancer enhances differentiation of protumorigenic Treg cells through a TNF/TNFR2/NF-κB signaling pathway in both human and mouse lung ADC. Depletion of one of the molecules that are required for Treg cell induction represses lung ADC development. Thus, the components that interfere with this particular Treg differentiation provide targets for the generation of TME-modifying therapies.
Topics & Concepts
ImmunologyLungBiologyCancer researchTreg cellMicrobiologyTumor microenvironmentImmune systemMedicineT cellIL-2 receptorInternal medicineNF-κB Signaling PathwaysImmune Cell Function and InteractionCancer Immunotherapy and Biomarkers