Targeting FAM83D triggers tumor cell senescence via cGAS-STING signaling activation and reprograms TAMs to combat glioma

Early human evidence such as case series or small samples is exploring possible benefits.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

BACKGROUND: Glioma, a prevalent and aggressive primary brain tumor, has a poor prognosis despite the administration of standard treatment. Cellular senescence is thought to have a good protective effect in limiting the malignant progression of tumors, while the senescence-associated secretory phenotype produced by senescent cells may influence the activity of immune cells in the microenvironment. Macrophages, as a major component of the glioma microenvironment, play an important role in regulating the innate and adaptive immune responses which is essential for tumor suppression. Therefore, identifying potential targets that connect tumor cell senescence with macrophage reprogramming may facilitate the development of new therapeutic agents in glioma. METHODS: Here, we developed the CellToAge algorithm and leveraged high-throughput sequencing data to map senescence-associated signatures in glioma. Based on in vitro and in vivo experiments including the cell co-culture model, in situ allograft mouse model, and single-cell transcriptome sequencing, we further elucidated the interplay between tumor cell senescence and macrophage polarization induced by knockdown of FAM83D in glioma. RESULTS: Notably, we identified the projected senescence-associated signatures in glioma (PSAG) and focused on the potential target FAM83D. In vitro and in vivo assays showed that knockdown of FAM83D res

Evidence level

Early human evidence such as case series or small samples is exploring possible benefits.

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