Tumor monocyte content predicts immunochemotherapy outcomes in esophageal adenocarcinoma

Journal article

For inoperable esophageal adenocarcinoma (EAC), identifying patients likely to benefit from recently approved immunochemotherapy (ICI+CTX) treatments remains a key challenge. We address this using a uniquely designed window-of-opportunity trial (LUD2015-005), in which 35 inoperable EAC patients received first-line immune checkpoint inhibitors for four weeks (ICI-4W), followed by ICI+CTX. Comprehensive biomarker profiling, including generation of a 65,000-cell single-cell RNA-sequencing atlas of esophageal cancer, as well as multi-timepoint transcriptomic profiling of EAC during ICI-4W, reveals a novel T cell inflammation signature (INCITE) whose upregulation correlates with ICI-induced tumor shrinkage. Deconvolution of pre-treatment gastro-esophageal cancer transcriptomes using our single-cell atlas identifies high tumor monocyte content (TMC) as an unexpected ICI+CTX-specific predictor of greater overall survival (OS) in LUD2015-005 patients and of ICI response in prevalent gastric cancer subtypes from independent cohorts. Tumor mutational burden is an additional independent and additive predictor of LUD2015-005 OS. TMC can improve patient selection for emerging ICI+CTX therapies in gastro-esophageal cancer.

Authors: Carroll, TM; Chadwick, JA; Owen, RP; White, MJ; Kaplinsky, J

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Cell Press
• Journal: Cancer Cell
• Volume: 41
• Issue: 7
• Pages: 1222–1241
• Publication date: 2023-07-10
• Acceptance date: 2023-06-14
• DOI: 10.1016/j.ccell.2023.06.006
• EISSN: 1878-3686
• ISSN: 1535-6108
• Pmid: 37433281
• Language: English
• Keywords: tumor associated monocytes; esophageal cancer; immune checkpoint inhibitors; cell type deconvolution; FFR; molecular profiling; immunochemotherapy; tumor mutational burden; immune priming; single-cell RNA-sequencing atlas; predictive biomarkers