Chromosomal instability shapes the tumor microenvironment of esophageal adenocarcinoma via a cGAS-chemokine-myeloid axis - PubMed
12 hours ago
- #cGAS-STING Pathway
- #Esophageal Adenocarcinoma
- #Chromosomal Instability
- Chromosomal instability (CIN) is a key feature of esophageal adenocarcinoma (EAC), driving tumor aggressiveness and metastasis.
- CIN activates the cGAS-STING pathway, which is usually associated with antitumor immunity, but remains intact in EAC despite high CIN.
- Myeloid-attracting chemokines, particularly CXCL8, are identified as conserved CIN-driven targets in EAC.
- Multiplexed immunofluorescence microscopy and whole-genome sequencing were used to quantify CIN in human EAC tumors.
- Single-nucleus RNA sequencing and multiplex immunophenotyping linked CIN to tumor-intrinsic innate immune activation and myeloid cell-mediated immunosuppression.
- CINhigh, myeloid-dominated EAC tumors correlate with poor patient outcomes and aberrant cGAS-STING signaling.
- Disrupting the CIN-cGAS-inflammation axis is proposed as a potential therapeutic strategy for EAC.
- Several authors have conflicts of interest, including advisory roles and research funding from pharmaceutical companies.