New research reveals that chromosomal instability in oesophageal adenocarcinoma is directly linked to tumour-driven immunosuppression and worse clinical outcomes. Despite activating the cGAS-STING pathway, which typically triggers anti-tumour immunity, these tumours maintain immune evasion.
Investigators identified myeloid-attracting chemokines, particularly CXCL8, as key targets of chromosomal instability. This suggests instability redirects immune signaling toward tumour-promoting inflammation.
Using multiplexed immunofluorescence microscopy and single-nucleus RNA sequencing, researchers quantified chromosomal instability and linked it to increased CXCL8 expression. Tumors with high instability showed myeloid cell dominance and immunosuppressive features, correlating with poor patient outcomes.
The findings suggest that disrupting the cGAS-chemokine-myeloid axis could restore effective immune responses and improve outcomes in oesophageal adenocarcinoma.