Coupling of response biomarkers between tumor and peripheral blood in patients undergoing chemoimmunotherapy. in Cell reports. Medicine / Cell Rep Med. 2025 Jan 21;6(1):101882. doi: 10.1016/j.xcrm.2024.101882. Epub 2024 Dec 27.

2025

Tipo pubblicazione

Clinical Trial, Phase II; Journal Article;

Autori/Collaboratori (30)Vedi tutti...

Lesterhuis WJ
National Centre for Asbestos Related Diseases, Institute for Respiratory Health, Nedlands, WA 6009, Australia; School of Biomedical Sciences, University of Western Australia, Crawley, WA 6009, Australia; The Kids Research Institute, University of Western Australia, Nedlands WA 6009, Australia. Electronic address: willem.lesterhuis@uwa.edu.au.
Lassmann T
The Kids Research Institute, University of Western Australia, Nedlands WA 6009, Australia. Electronic address: timo.lassmann@thekids.org.au.
Nowak AK
National Centre for Asbestos Related Diseases, Institute for Respiratory Health, Nedlands, WA 6009, Australia; Medical School, University of Western Australia, Crawley, WA 6009, Australia; Department of Medical Oncology, Sir Charles Gairdner Hospital, Nedlands, WA 6009, Australia. Electronic address: anna.nowak@uwa.edu.au.

et alii...

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.

PMID : 39731918

DOI : 10.1016/j.xcrm.2024.101882

Keywords

Middle Aged; Transcriptome/genetics; Neoplasms/drug therapy/blood/immunology; Receptors, Antigen, T-Cell/metabolism; Female; Male; Leukocytes, Mononuclear/metabolism; CD8-Positive T-Lymphocytes/immunology/metabolism; Tumor Microenvironment/immunology; Immunotherapy/methods; Biomarkers, Tumor/blood; Humans;