Cell reports. Medicine · 2024
Coupling of response biomarkers between tumor and peripheral blood in patients undergoing chemoimmunotherapy.
СтатьяКлиническое исследование II фазыНазвание и аннотация: Перевод пока не подготовлен
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Chin Wee Loong, Cook Alistair M, Chee Jonathan, Principe Nicola, Hoang Tracy S, Kidman Joel, Hmon Khaing P W, Yeow Yen, Jones Matthew E, Hou Rui, Denisenko Elena, McDonnell Alison M, Hon Chung-Chau, Moody Jonathan, Anderson Denise, Yip Sonia, Cummins Michelle M, Stockler Martin R, Kok Peey-Sei, Brown Chris, John Thomas, Kao Steven C-H, Karikios Deme J, O'Byrne Kenneth J, Hughes Brett G M, Lake Richard A, Forrest Alistair R R, Nowak Anna K, Lassmann Timo, Lesterhuis W Joost
Аннотация
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.