食道がんの一部が治療困難な理由を解明（New research reveals why some oesophageal cancers are so hard to treat）

2026-03-13 オックスフォード大学

＜関連情報＞

• https://www.ox.ac.uk/news/2026-03-13-new-research-reveals-why-some-oesophageal-cancers-are-so-hard-treat
• https://www.science.org/doi/10.1126/sciadv.aeb1611

染色体不安定性は、cGAS-ケモカイン-骨髄系軸を介して食道腺癌の腫瘍微小環境を形成する Chromosomal instability shapes the tumor microenvironment of esophageal adenocarcinoma via a cGAS–chemokine–myeloid axis

Bruno Beernaert, Rose L. Jady-Clark, Parin Shah, Erik Ramon-Gil, […] , and Eileen E. Parkes
Science Advances  Published:11 Mar 2026

Abstract

Chromosomal instability (CIN), a pervasive feature of esophageal adenocarcinoma (EAC), drives tumor aggressiveness and metastasis. CIN stimulates the cGAS–STING pathway, typically linked to antitumor immunity. However, despite the high CIN burden in EAC, the cGAS–STING pathway remains largely intact. To address this paradox, we interrogated multiple esophageal cancer models, finding myeloid-attracting chemokines—with CXCL8 as a prominent hit—as conserved CIN-driven targets in EAC. Using multiplexed immunofluorescence microscopy, we quantified ongoing CIN in human EAC tumors by measuring cGAS-positive micronuclei, validated by whole-genome sequencing. Coupling in situ CIN detection with single-nucleus RNA sequencing and multiplex immunophenotyping of human EAC, we link CIN to tumor-intrinsic innate immune activation, CXCL8 expression, and myeloid cell–mediated immunosuppression. In patients with EAC, CIN^high, myeloid-dominated tumors correlate with poor outcomes and aberrant cGAS–STING signaling. These insights explain the counterintuitive maintenance of cGAS–STING and highlight the disruption of the CIN–cGAS–inflammation axis as a potential therapeutic strategy in EAC.