Coupling of response biomarkers between tumor and peripheral blood in patients undergoing chemoimmunotherapy.

IF 11.7 1区医学 Q1 CELL BIOLOGY

Cell Reports Medicine Pub Date : 2025-01-21 Epub Date: 2024-12-27 DOI:10.1016/j.xcrm.2024.101882

Wee Loong Chin, Alistair M Cook, Jonathan Chee, Nicola Principe, Tracy S Hoang, Joel Kidman, Khaing P W Hmon, Yen Yeow, Matthew E Jones, Rui Hou, Elena Denisenko, Alison M McDonnell, Chung-Chau Hon, Jonathan Moody, Denise Anderson, Sonia Yip, Michelle M Cummins, Martin R Stockler, Peey-Sei Kok, Chris Brown, Thomas John, Steven C-H Kao, Deme J Karikios, Kenneth J O'Byrne, Brett G M Hughes, Richard A Lake, Alistair R R Forrest, Anna K Nowak, Timo Lassmann, W Joost Lesterhuis

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引用次数: 0

Abstract

Platinum-based chemotherapy in combination with anti-PD-L1 antibodies has shown promising results in mesothelioma. However, the immunological mechanisms underlying its efficacy are not well understood and there are no predictive biomarkers to guide treatment decisions. Here, we combine time course RNA sequencing (RNA-seq) of peripheral blood mononuclear cells with pre-treatment tumor transcriptome data from the single-arm, phase 2 DREAM trial (N = 54). Single-cell RNA-seq and T cell receptor sequencing (TCR-seq) reveal that CD8⁺ T effector memory (TEM) cells with stem-like properties are more abundant in peripheral blood of responders and that this population expands upon treatment. These peripheral blood changes are linked to the transcriptional state of the tumor microenvironment. Combining information from both compartments, rather than individually, is most predictive of response. Our study highlights complex interactions between the tumor and immune cells in peripheral blood during objective tumor responses to chemoimmunotherapy. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12616001170415.

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化疗免疫治疗患者肿瘤与外周血反应生物标志物的耦合

以铂为基础的化疗联合抗pd - l1抗体治疗间皮瘤已显示出良好的效果。然而，其疗效背后的免疫学机制尚不清楚，也没有预测性的生物标志物来指导治疗决策。在这里，我们将外周血单个核细胞的时间过程RNA测序（RNA-seq）与单臂2期DREAM试验（N = 54）的治疗前肿瘤转录组数据结合起来。单细胞RNA-seq和T细胞受体测序（TCR-seq）显示，具有干细胞样特性的CD8+ T效应记忆（TEM）细胞在应答者的外周血中更为丰富，并且这一群体在治疗后会扩大。这些外周血变化与肿瘤微环境的转录状态有关。结合两个部分的信息，而不是单独的信息，最能预测反应。我们的研究强调了在肿瘤对化学免疫治疗的客观反应中，肿瘤和外周血免疫细胞之间复杂的相互作用。该试验已在澳大利亚新西兰临床试验注册中心注册，编号为ACTRN12616001170415。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell Reports Medicine Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)

CiteScore

15.00

自引率

1.40%

发文量

231

审稿时长

40 days

期刊介绍： Cell Reports Medicine is an esteemed open-access journal by Cell Press that publishes groundbreaking research in translational and clinical biomedical sciences, influencing human health and medicine. Our journal ensures wide visibility and accessibility, reaching scientists and clinicians across various medical disciplines. We publish original research that spans from intriguing human biology concepts to all aspects of clinical work. We encourage submissions that introduce innovative ideas, forging new paths in clinical research and practice. We also welcome studies that provide vital information, enhancing our understanding of current standards of care in diagnosis, treatment, and prognosis. This encompasses translational studies, clinical trials (including long-term follow-ups), genomics, biomarker discovery, and technological advancements that contribute to diagnostics, treatment, and healthcare. Additionally, studies based on vertebrate model organisms are within the scope of the journal, as long as they directly relate to human health and disease.