英国牛津大学Xin Lu和Mark R. Middleton团队合作利用单核细胞含量(TMC)预测食管腺癌(EAC)免疫化疗结果。这一研究成果于2023年7月10日发表在国际顶尖学术期刊《癌细胞》上。

他们进行了一项独特设计的机会之窗试验(LUD2015-005)，其中35名不能手术的EAC患者接受了为期四周的一线免疫检查点抑制剂(ICI-4W)，然后是免疫化疗(ICI+CTX)。综合生物标志物分析，包括生成65000个食管癌单细胞RNA测序图谱，以及ICI-4W期间EAC的多时间点转录组学分析，揭示了一种新的T细胞炎症特征(INCITE)，其上调与ICI诱导的肿瘤缩小相关。

使用他们的单细胞图谱对治疗前胃食管癌转录组进行反卷积，发现高TMC是LUD2015-005患者更高总生存率(OS)，和独立队列中流行胃癌亚型ICI反应的意外ICI+CTX特异性预测因子。肿瘤突变负荷是LUD2015-005 OS的另一个独立和累加的预测因子。TMC可以改善胃食管癌患者对新出现的ICI+CTX治疗的选择。

据介绍，对于不能手术的EAC，确定可能从最近批准的ICI+CTX治疗中获益的患者仍然是一个关键挑战。

附：英文原文

Title: Tumor monocyte content predicts immunochemotherapy outcomes in esophageal adenocarcinoma

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

Issue&Volume: 2023/07/10

Abstract: 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.

DOI: 10.1016/j.ccell.2023.06.006

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(23)00216-7