Anti-PD-1 therapy has left an indelible mark in the field of non-small-cell lung cancer (NSCLC) treatment; however, its efficacy is limited in clinical practice owing to differences in the degree of effector T-cell exhaustion. Casein kinase 2 (CK2) is a protein kinase that plays an important role in T-cell immunity. In this study, it is aimed to explore the potential of targeting CK2 and its regulatory subunit CK2B to prevent or reverse T-cell exhaustion, thereby enhancing the efficacy of anti-PD-1 therapy in NSCLC. In this study, it is found that CK2B expression is closely associated with T-cell exhaustion as well as the efficacy of anti-PD-1 therapy based on scRNA-seq and in vitro and in vivo experiments. Uti... More
Anti-PD-1 therapy has left an indelible mark in the field of non-small-cell lung cancer (NSCLC) treatment; however, its efficacy is limited in clinical practice owing to differences in the degree of effector T-cell exhaustion. Casein kinase 2 (CK2) is a protein kinase that plays an important role in T-cell immunity. In this study, it is aimed to explore the potential of targeting CK2 and its regulatory subunit CK2B to prevent or reverse T-cell exhaustion, thereby enhancing the efficacy of anti-PD-1 therapy in NSCLC. In this study, it is found that CK2B expression is closely associated with T-cell exhaustion as well as the efficacy of anti-PD-1 therapy based on scRNA-seq and in vitro and in vivo experiments. Utilization of CK2 inhibitors or knockdown of CK2B expression can upregulate TBX21 expression through HDAC8-mediated epigenetic reprogramming, restoring the effector function of CD8+ T cells and enhancing the efficacy of anti-PD-1 therapy in NSCLC. These findings underscore CK2B as a promising target for overcoming the exhaustion of effector CD8+ T cells, thereby enhancing the efficacy of anti-PD-1 and adoptive cell therapies in NSCLC. Moreover, CK2B expression serves as a novel predictor of immunotherapy efficacy for NSCLC.
