The enhancement of immunoactivity induced by immunogenic cell death through serine/threonine kinase 10 inhibition: a potential therapeutic strategy

通过抑制丝氨酸/苏氨酸激酶 10 增强免疫原性细胞死亡诱导的免疫活性:一种潜在的治疗策略

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作者:Xiaoli Xia #, Yixin Wang #, Minghui Wang #, Jian Lin, Ruiheng Wang, Shufeng Xie, Yaoyifu Yu, Jinlan Long, Zixuan Huang, Huajian Xian, Wenjie Zhang, Chaoqun Lu, Wenfang Wang, Han Liu

Discussion

In the ICD-high subtype, there was a notable increase in the abundance of immune cell populations, along with the enrichment of pathways pertinent to the activation of various immune cells. Despite these immunological enhancements, this subgroup demonstrated a poorer prognosis. This phenomenon was consistently observed across various additional AML datasets, leading us to hypothesize that elevated expression of ICD genes does not invariably correlate with a favorable prognosis. Notably, STK10 exhibited elevated expression in AML, was associated with a poor prognosis, and showed synchronous expression patterns with ICD genes. Inhibition of STK10 led to the activation of ICD and the induction of an antitumor response. Moreover, when combined with other ICD inducers, it produced a synergistic anti-tumor effect. Our results reveal the impact of STK10 on ICD and underscore its key role in initiating ICD.

Methods

Through cluster analysis, patient specimens retrieved from the TARGET, TCGA, and GEO AML databases were categorized into two subtypes based on the expression levels of ICD-related genes: ICD-high and ICD-low. We compared the prognostic survival outcomes, pathway enrichment analysis, and immune cell infiltration between these two subtypes. Additionally, we identified factors related to AML development from multiple databases and verified the role of these factors both in vivo and in vitro in activating the immune response during the occurrence of ICD.

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