The abstract is read at the publisher; the summary is JClub's.
Stk11 loss in Kras-mutant murine lung models promotes NETosis via the complement C5a–C5aR1 axis, creating an immunosuppressive TME that resists PD-1/PD-L1 blockade.
- Why it matters: KRAS/STK11-mutant LUADs are clinically aggressive and show primary resistance to immune checkpoint inhibitors, but the immune-evasion mechanism is not fully defined.
- What they did: In a multicenter human LUAD cohort, integrative genomic and immunophenotypic profiling linked KRAS/STK11 co-mutation to NET formation, neutrophil enrichment, and reduced CD8+ T-cell infiltration. In immunocompetent Kras-mutant murine models, Stk11 loss was tested for NETosis and complement C5a–C5aR1 signaling, with pharmacologic C5a inhibition.
- The result: Blocking C5a signaling suppressed NETosis, reduced tumor growth, and restored T-cell infiltration in KS tumors, supporting C5a–C5aR1 as a therapeutically actionable vulnerability.
The findingWhy it mattersWhat they didThe result
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