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Combination of a CCL21-gene modified dendritic cell vaccine and pembrolizumab induces immune responses in non-small cell lung cancer

GSE317309 Homo sapiens; Mus musculus Expression profiling by high throughput sequencing 64 samples Submitted 2026/05/01 Platform GPL34284Platform GPL35012
Summary
Immune checkpoint inhibitors (ICIs) have transformed treatment for non-small cell lung cancer (NSCLC), but resistance to these therapies is common. We report results from a phase I trial combining intratumoral administration of a CCL21-gene modified dendritic cell (CCL21-DC) vaccine with pembrolizumab in patients with advanced NSCLC. Among 23 patients that received trial therapy, there were no dose-limiting toxicities and a low incidence of treatment-related adverse events. Although no objective responses were observed, 36.8% of patients had a best response of stable disease (SD). Correlative analyses of longitudinal tumor biopsies revealed that disease stability was associated with reduced tumor mutational heterogeneity and increased intratumoral T cell receptor diversity following therapy. Post-treatment tumor biopsies exhibited increased CD4+ T cell infiltration and the presence of novel T cell clones that predominantly possessed CD4+ memory T cell phenotypes. These novel clones experienced greater clonal expansion and a transition towards exhausted phenotypes in SD samples. However, many novel clones failed to persist over time, and immunosuppressive myeloid signaling signatures were identified especially in progressive disease samples. Our findings demonstrated that CCL21-DC vaccination combined with pembrolizumab is safe and can promote antitumor immune responses in a subset of patients. However, efficacy may have been constrained due to limited tumor specificity of the T cell response and an inability to fully reprogram the immunosuppressive tumor microenvironment.
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Direct links to NCBI, no account and no request form: the whole study as GSE317309_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 64 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1348488 and SRA study SRP663891. Searching any of these in the dataset finder brings you back here.

Study design
9 conditions, mostly in duplicate
Patient DCP09, 10x Genomics 5' V(D)J sequenci… ×3 Patient DCP10, 10x Genomics 5' V(D)J sequenci… ×3 Patient DCP14, 10x Genomics 5' V(D)J sequenci… ×3 Patient DCP12, 10x Genomics 5' V(D)J sequenci… ×2 Patient DCP16, 10x Genomics 5' V(D)J sequenci… ×2 Patient DCP17, 10x Genomics 5' V(D)J sequenci… ×2 Patient DCP18, 10x Genomics 5' V(D)J sequenci… ×2 Patient DCP19, 10x Genomics 5' V(D)J sequenci… ×2 +20 more

Supports a between-group comparison across 21 samples.

9 replicated groups read from the first 40 of 64 sample titles; they account for 21 of them. Check it against the sample list below before relying on it.

Samples in this study

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