The gastric oncobacterium Streptococcus anginosus drives tumor progression and immune evasion through extracellular vesicle-mediated delivery of the bacterial chromatin remodeler saSNF2, which integrates into host BAF complexes and cooperates with TEAD1 to upregulate the palmitoyltransferase ZDHHC11, thereby stabilizing PD-L1 via palmitoylation at Cys272 to suppress CD8+ T cell function—a mechanism that can be therapeutically targeted by combining palmitoylation inhibitors with anti-PD-1 checkpoint blockade.

Emerging evidence highlights the crucial role of microbial communities in modulating cancer development and progression. In gastric cancer (GC), we identify Streptococcus anginosus (SA) as a tumor-resident oncobacterium that drives both tumor progression and immune evasion. We define a novel mechanism in which SA secretes extracellular vesicles (saEVs) that translocate the bacterial chromatin remodeler saSNF2 into host cell. There, saSNF2 partners with host transcription factor TEAD1—through its ATPase activity and participation in BAF complex assembly—to coordinately activate oncogenic transcription. This transkingdom interaction upregulates the palmitoyltransferase ZDHHC11, which in turn stabilizes PD-L1 via palmitoylation to establish an immunosuppressive niche, while also amplifying other TEAD1 target genes to fuel tumor progression. Functionally, saEVs promote tumor growth and limit CD8+ T-cell infiltration in vivo. Strikingly, pharmacological inhibition of ZDHHC11 reverses immune evasion and synergizes with anti-PD-1 checkpoint blockade. Our results establish SA as a multifaceted driver of GC and reveal the saSNF2-ZDHHC11 axis as a promising target to potentiate immunotherapy.