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)Elenco ridotto...

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.
Forrest ARR
Harry Perkins Institute of Medical Research, QEII Medical Centre and Centre for Medical Research, The University of Western Australia, Nedlands, Perth, WA 6009, Australia. Electronic address: alistair.forrest@gmail.com.
Lake RA
National Centre for Asbestos Related Diseases, Institute for Respiratory Health, Nedlands, WA 6009, Australia; Medical School, University of Western Australia, Crawley, WA 6009, Australia.
O'Byrne KJ
Department of Medical Oncology, Princess Alexandra Hospital, Brisbane, QLD, Australia.
Hughes BGM
Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia; School of Medicine, University of Queensland, Brisbane, QLD, Australia.
Karikios DJ
Department of Medical Oncology, Nepean Hospital, Kingswood, NSW, Australia.
Brown C
National Health and Medical Research Council, Clinical Trials Centre, University of Sydney, Camperdown, NSW, Australia.
John T
Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
Kao SC
Department of Medical Oncology, Chris O'Brien Lifehouse, Camperdown, NSW, Australia.
Kok PS
National Health and Medical Research Council, Clinical Trials Centre, University of Sydney, Camperdown, NSW, Australia.
Anderson D
The Kids Research Institute, University of Western Australia, Nedlands WA 6009, Australia.
Yip S
National Health and Medical Research Council, Clinical Trials Centre, University of Sydney, Camperdown, NSW, Australia.
Cummins MM
National Health and Medical Research Council, Clinical Trials Centre, University of Sydney, Camperdown, NSW, Australia.
Stockler MR
National Health and Medical Research Council, Clinical Trials Centre, University of Sydney, Camperdown, NSW, Australia.
Moody J
RIKEN Center for Integrative Medical Sciences, Yokohama City, Kanagawa 230-0045, Japan.
Hon CC
RIKEN Center for Integrative Medical Sciences, Yokohama City, Kanagawa 230-0045, Japan.
McDonnell AM
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.
Denisenko E
Harry Perkins Institute of Medical Research, QEII Medical Centre and Centre for Medical Research, The University of Western Australia, Nedlands, Perth, WA 6009, Australia.
Hou R
Harry Perkins Institute of Medical Research, QEII Medical Centre and Centre for Medical Research, The University of Western Australia, Nedlands, Perth, WA 6009, Australia.
Jones ME
Harry Perkins Institute of Medical Research, QEII Medical Centre and Centre for Medical Research, The University of Western Australia, Nedlands, Perth, WA 6009, Australia.
Yeow Y
Harry Perkins Institute of Medical Research, QEII Medical Centre and Centre for Medical Research, The University of Western Australia, Nedlands, Perth, WA 6009, Australia.
Hmon KPW
Harry Perkins Institute of Medical Research, QEII Medical Centre and Centre for Medical Research, The University of Western Australia, Nedlands, Perth, WA 6009, Australia.
Chee J
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.
Principe N
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.
Hoang TS
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.
Kidman J
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.
Chin WL
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.
Cook AM
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.

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;