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

Cite

Chin, W.L., Cook, A.M., Chee, J., Principe, N., Hoang, T.S., Kidman, J., Hmon, K.P., Yeow, Y., Jones, M.E., Hou, R. and Denisenko, E., 2025. Coupling of response biomarkers between tumor and peripheral blood in patients undergoing chemoimmunotherapy. Cell Reports Medicine, 6(1). https://doi.org/10.1016/j.xcrm.2024.101882

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.

Datasets

1. DREAM scRNA-seq

Explore
Cell type
Sample ID
Progression-free survival at 6 months
Timepoint
Sample name
GEO accession
Tissue
Cell line
Response (PFS6M)
Subject ID
Treatment
Disease
Assay
Sample preservation method
Reference genome
Age
CD14 Mono102,786 cells
CD4 TCM80,690 cells
NK54,067 cells
CD8 TEM44,982 cells
CD4 Naive24,917 cells
CD16 Mono17,563 cells
B naive12,779 cells
CD8 Naive6,215 cells
CD4 TEM5,714 cells
Treg5,341 cells
B intermediate4,608 cells
CD4 CTL3,860 cells
MAIT3,709 cells
Platelet3,501 cells
cDC23,165 cells
CD8 TCM2,312 cells
Plasmablast1,854 cells
B memory1,833 cells
pDC1,827 cells
gdT1,445 cells
NK_CD56bright1,405 cells
HSPC1,010 cells
dnT947 cells
Doublet840 cells
CD4 Proliferating726 cells
NK Proliferating565 cells
Eryth542 cells
ILC410 cells
CD8 Proliferating310 cells
cDC1276 cells
ASDC174 cells
Coupling of response biomarkers between tumor and peripheral blood in patients undergoing chemoimmunotherapy

2. DREAM bulk RNA-seq

Explore
Leiden clustering
Sample ID
Sample name
GEO accession
Sample source
Tissue
Cell type
Response (PFS6M)
Disease
Assay
Sample preservation method
Age
Treatment
Subject ID
Timepoint
Cluster 230 cells
Cluster 126 cells
Cluster 521 cells
Cluster 620 cells
Cluster 313 cells
Cluster 410 cells
Coupling of response biomarkers between tumor and peripheral blood in patients undergoing chemoimmunotherapy

3. DREAM NanoString

Explore
Leiden clustering
Sample name
Sample ID
Date
Gene RLF
System APF
Assay
Subject ID
GEO accession
Sample source
Batch ID
Lane ID
Tissue
Sex
Histology
Progression-free at 6 months
Sample preservation method
Disease
Age
Treatment
Cluster 221 cells
Cluster 114 cells
Cluster 311 cells
Coupling of response biomarkers between tumor and peripheral blood in patients undergoing chemoimmunotherapy

Alias names

GSE252990, GSE253173, GSE248514, GSE252432