Portal de Periódicos da CAPES

Tumor monocyte content predicts immunochemotherapy outcomes in esophageal adenocarcinoma

2023; Cell Press; Volume: 41; Issue: 7 Linguagem: Inglês

10.1016/j.ccell.2023.06.006

1878-3686

Thomas Carroll, Joseph A. Chadwick, Richard Owen, Michael J. White, Joseph Kaplinsky, Iliana Peneva, Anna Frangou, Phil F. Xie, Jaeho Chang, Andrew Roth, Bob Amess, Sabrina A. James, Margarida Rei, Hannah S. Fuchs, Katy J. McCann, Ayo O. Omiyale, Brittany‐Amber Jacobs, Simon Lord, Stewart Norris-Bulpitt, Sam T. Dobbie, Lucinda Griffiths, Kristen Aufiero Ramirez, Toni Ricciardi, Mary Macri, Aileen Ryan, Ralph Venhaus, Benoı̂t J. Van den Eynde, Ioannis Karydis, Benjamin Schuster‐Böckler, Mark R. Middleton, Xin Lü, David Ahern, Bob Amess, Kristen Aufiero Ramirez, G. Berridge, Thomas Carroll, Joseph A. Chadwick, Jaeho Chang, Jingfei Cheng, Sam T. Dobbie, Magdalena Dróżdż, Román Fischer, Anna Frangou, Hannah S. Fuchs, Lucinda Griffiths, Masato Inoue, Brittany‐Amber Jacobs, Sabrina A. James, Joseph Kaplinsky, Ioannis Karydis, Benedikt M. Kessler, Simon Lord, Hantao Lou, Xin Lü, Mary Macri, Katy J. McCann, Naomi McGregor, Mark R. Middleton, Stewart Norris-Bulpitt, Ayo O. Omiyale, Richard Owen, Iliana Peneva, Chansavath Phetsouphanh, Margarida Rei, Toni Ricciardi, Andrew Roth, Carlos Ruiz de Alegría Puig, Aileen Ryan, Benjamin Schuster‐Böckler, Paulina Siejka-Zielińska, Chunxiao Song, Markéta Tomková, Benoı̂t J. Van den Eynde, Gergana Velikova, Ralph Venhaus, Michael J. White, Phil F. Xie,

Pancreatic and Hepatic Oncology Research

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.