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| Status |
Public on Apr 05, 2023 |
| Title |
The utility of circulating CX3CR1+ CD8+ T cells as a predictive correlate of response to chemo-immunotherapy in patients with non-small cell lung cancer |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Other
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| Summary |
Lack of reliable predictive biomarkers is a major limitation of combination therapy with chemotherapy and anti-PD-1 therapy (chemo-immunotherapy). The increase of peripheral blood (PB) CD8+ T cells expressing CX3CR1, a marker of differentiation, correlates with response to anti-PD-1 therapy; however, the predictive and prognostic value of T-cell CX3CR1 expression during chemo-immunotherapy remains elusive. Here, we evaluated the utility of PB CX3CR1+CD8+ T cells as a predictive correlate of response to chemo-immunotherapy in non-small cell lung cancer (NSCLC) patients. At least 10% increase of the CX3CR1+ subset in circulating CD8+ T cells from baseline (CX3CR1 score) was associated with response to chemo-immunotherapy at 6 weeks (p = 0.0382) and 9 weeks (p = 0.0045). Sensitivity, specificity, positive and negative predictive value of at least 10% increase of the CX3CR1 score was 83.3%, 88.2%, 83.3% and 88.2%, respectively with 86.2% overall accuracy of predicting response at 9 weeks. Furthermore, at least 10% increase of the CX3CR1 score correlated with improved overall (p = 0.0105) and progression-free survival (p = 0.0265). Combined T-cell receptor (TCR) sequencing of tumor tissue and single-cell RNA/TCR sequencing of longitudinal PB samples from a patient who received a long-term benefit from chemo-immunotherapy demonstrated that circulating clonally expanded CD8+ T cells were terminal effector T cells expressing high levels of CX3CR1, and contained frequent tumor-infiltrating T-cell colonotypes early-on post treatment. Collectively, these findings suggest the potential utility of T-cell CX3CR1 expression as a dynamic blood-based biomarker during the course of chemo-immunotherapy and a marker to identify frequent tumor-infiltrating lymphocyte repertoires.
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| Overall design |
Single live CD45+CD19–CD3+CD56– cells were enriched from cryopreserved PBMC samples obtained pre-treatment and on-treatment at 3, 6, 9 weeks by flow cytometry sorting using a BD FACSAria II (BD Biosciences). Cells were counted, hashed with TotalSeq-C0251, TotalSeq-C0252, TotalSeq-C0253 and TotalSeq-C0254 anti-human antibodies, BioLegend) and pooled. The pooled cells were then counted again and immediately loaded onto the chromium chip G using the standard protocol for the Chromium single-cell 5’ kit v2 (10x Genomics, Inc). Following Gel Bead-in Emulsion (GEM) generation, samples were processed using the standard manufacturer’s protocol. Once sequencing libraries passed standard quality control metrics, the libraries were sequenced on Illumina NovaSeq6000 S1 100cycle v1.5 kits with the following read structure: read1: 28, read2: 90, index 1: 10, index 2:10. Libraries were sequenced to obtain a read depth greater than 16,000 reads/cell for the gene-expression (GEX) libraries and greater than 4,000 reads/cell for the V(D)J-enriched T Cell libraries.
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| Contributor(s) |
Mark L, Fumito I |
| Citation(s) |
37009132 |
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| Submission date |
Sep 21, 2022 |
| Last update date |
Apr 05, 2023 |
| Contact name |
Mark D Long |
| E-mail(s) |
[email protected]
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| Organization name |
Roswell Park Comprehensive Cancer Center
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| Department |
Bioinformatics & Biostatistics
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| Street address |
Elm & Carlton Streets
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| City |
Buffalo |
| State/province |
NY |
| ZIP/Postal code |
14263 |
| Country |
USA |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA882907 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE213902_MQpool1_barcodes.tsv.gz |
19.8 Kb |
(ftp)(http) |
TSV |
| GSE213902_MQpool1_features.tsv.gz |
325.7 Kb |
(ftp)(http) |
TSV |
| GSE213902_MQpool1_filtered_contig_annotations.csv.gz |
353.0 Kb |
(ftp)(http) |
CSV |
| GSE213902_MQpool1_matrix.mtx.gz |
16.7 Mb |
(ftp)(http) |
MTX |
| GSE213902_MQpool2_barcodes.tsv.gz |
25.1 Kb |
(ftp)(http) |
TSV |
| GSE213902_MQpool2_features.tsv.gz |
325.7 Kb |
(ftp)(http) |
TSV |
| GSE213902_MQpool2_filtered_contig_annotations.csv.gz |
491.3 Kb |
(ftp)(http) |
CSV |
| GSE213902_MQpool2_matrix.mtx.gz |
21.6 Mb |
(ftp)(http) |
MTX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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