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Tumor-resident T cells and dendritic cells form an in situ archetype for immunotherapy response in melanoma [bulk RNA-seq]

GSE294272 Homo sapiens Expression profiling by high throughput sequencing 29 samples Submitted 2026/06/08 Platform GPL24676
Summary
Tumor-resident (TR) T cells participate in immunosurveillance of melanoma, but their role in determining response to immune checkpoint inhibitors (ICI) has not been comprehensively explored. We performed spatial and single-cell profiling on 32 metastatic melanoma lymph node samples, from treatment-naïve, ICI-resistant, or ICI-responsive patients. In responders, we found enrichment for early differentiation (TCF1+) CD8+ and CD4+ TR which co-localized with melanoma cells. CD8+ TR were hyperexpanded, and both CD8+ and CD4+ TR upregulated cytotoxicity-related gene expression, suggesting functional anti-tumor immunity. Conversely, ICI-resistant tumors displayed chronic IFN-γ responses within the tumor microenvironment to potentiate T cell exhaustion. In ICI-responsive melanoma tumors, CD8⁺ TR interact with CD4⁺ TR cells (via the CCL4-CCR5 axis) and engage with type-3 dendritic cells (DC3) (via IL15-IL15R interaction). This intratumoral immune triad (CD8⁺ TR – CD4⁺ TR – DC) is exclusive to responders. This study illustrates the role of TR cells and their crosstalk with DCs in effective ICI responses.
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Direct links to NCBI, no account and no request form: the whole study as GSE294272_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 29 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1248920. Searching any of these in the dataset finder brings you back here.

Study design
29 conditions, each sampled once — no replicated groups

Read from 29 sample titles: 29 distinct titles with little repetition. Check it against the sample list below before relying on it.

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