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

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<sup>+</sup> 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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Publication Details

Journal
Cell Reports Medicine
Published
2024-12-27
DOI
https://doi.org/10.1016/j.xcrm.2024.101882
Citations
6
Primary Topic
Cancer Immunotherapy and Biomarkers
Type
article
Field-Weighted Citation Impact
1.70

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article

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

Sonia Yip, Yen Yeow, W. Joost Lesterhuis, Wee Loong Chin et al.
6 citations
Cell Reports Medicine
Cancer Immunotherapy and Biomarkers
1.70
article

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

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

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<sup>+</sup> 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.

Cell Reports MedicineVol. 6(1)
The University of Sydney (AU), The Kids Research Institute Australia (AU), The University of Western Australia (AU), Royal Brisbane and Women's Hospital (AU), Harry Perkins Institute of Medical Research (AU), Peter MacCallum Cancer Centre (AU), Nepean Hospital (AU), Princess Alexandra Hospital (AU), Sir Charles Gairdner Hospital (AU), Queen Elizabeth II Medical Centre (AU), Chris O’Brien Lifehouse (AU), Keogh Institute for Medical Research (AU), Institute for Respiratory Health (AU), RIKEN Center for Integrative Medical Sciences (JP), National Health and Medical Research Council (AU)
U.S. Department of Defense, Mesothelioma Applied Research Foundation, AstraZeneca, Lee Foundation, Australian Government, Simon Lee Foundation, Australian Cancer Research Foundation, Raine Medical Research Foundation, New South Wales Workers' Compensation Dust Disease Board, University of Sydney, Department of Health, Government of Western Australia, Government of Western Australia, Medical Research Council, National Health and Medical Research Council, Cancer Council Western Australia
Good health and well-being
Openalex Percentile: Top 12%
Cancer Immunotherapy and Biomarkers
1.70
DOIOpen Access PDFOpenAlex
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