Glycosphingolipid synthesis mediates immune evasion in KRAS-driven cancer.

Nature. 2024 Sep;633(8029):451-458.

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Significance :

This study employs functional genomics and lipidomic approaches to identify de novo sphingolipid synthesis

as a key pathway in cancer immune evasion. Additionally, it reveals that glycosphingolipid synthesis promotes

immune evasion by modulating the surface expression of IFNGR1, aligning with the crucial role of IFNγ

signaling in immune surveillance and immunotherapy effectiveness.

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Importance of lipidology :

By knocking out sptlc1 in a Kras-mutant mouse pancreatic ductal adenocarcinoma (PDAC) cell line,

the study demonstrates its role in promoting immune evasion through the IFNγ signaling pathway,

impacting NK and CD8+ T cell immune surveillance.

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Connectivity to other field :

By exploring genes involved in lipid metabolism pathways, the study aims to identify new prognostic factors

for Kras-mutant driven cancers. These findings could ultimately enhance the effectiveness of current

checkpoint blockade therapies by leveraging this potential prognostic factor.

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https://pubmed.ncbi.nlm.nih.gov/39112706/

Lipid Profiling

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