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Tumor-resident T cells and dendritic cells form an in situ archetype during immunotherapy response in melanoma.

Tumor-resident (TR) T cells, known as tissue-resident memory (TRM) T cells in mice, play a central role in melanoma immunosurveillance, yet their contribution to immune checkpoint inhibitors (ICI) therapy 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. Here we show that tumor areas in ICI-responders were enriched in both CD8+ and CD4+ TR. CD8+ TR were hyperexpanded, and both CD8+ and CD4+ TR cells upregulated cytotoxicity-related gene expression, suggesting functional anti-tumor immunity. Conversely, ICI-resistant tumors displayed chronic IFN-γ response pathways, linked to T cell exhaustion. We further identified a spatially organized immune triad composed of CD8⁺ TR, CD4⁺ TR, and type-3 dendritic cells (DC3) that is exclusive to responding tumors. These findings define coordinated cellular interactions within the tumor microenvironment that underpin successful immunotherapy and provide a framework for spatial biomarkers of response.

Type: Transcriptome Sequencing
Archiver: European Genome-phenome Archive (EGA)

4 Datasets

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID	Description	Technology	Samples
EGAD50000002475	This dataset comprises raw FASTQ files from bulk RNA sequencing of metastatic melanoma lymph node samples collected from patients with differential responses to immune checkpoint inhibitor therapy. RNA was extracted from tumour tissue, enriched for polyadenylated transcripts, and libraries were prepared using standard Illumina protocols. Sequencing was performed on an Illumina platform to generate high-quality paired-end reads. The dataset includes multiple patient samples with associated clinical annotations, enabling analysis of tumour-intrinsic transcriptional programs linked to immunotherapy response and resistance.	NextSeq 2000	29
EGAD50000002476	This dataset comprises raw FASTQ files generated from single-cell RNA sequencing of metastatic melanoma lymph node samples using the 10x Genomics Chromium platform. Single-cell suspensions were prepared from tumour tissues, and libraries were constructed using 5′ or 3′ gene expression kits following the manufacturer’s protocol. Sequencing was performed on an Illumina platform to obtain high-throughput single-cell transcriptomic profiles. The dataset includes samples from patients with differing responses to immune checkpoint inhibitor therapy, enabling characterisation of tumour-resident immune cell populations and tumour–immune interactions associated with treatment response and resistance.	Illumina NovaSeq 6000	12
EGAD50000002477	This dataset comprises gene expression data generated using the Nanostring nCounter platform from metastatic melanoma samples. RNA extracted from tumour tissues was analysed using targeted gene expression panels, including immune-related and tumour-resident T cell signatures. The dataset includes RCC files and associated normalised counts derived from patients with differing responses to immune checkpoint inhibitor therapy. These data enable targeted profiling of immune and tumour transcriptional programs associated with treatment response and resistance.	unspecified	23
EGAD50000002478	This dataset comprises raw FASTQ files generated from T cell receptor (TCR) sequencing of metastatic melanoma samples using the 10x Genomics V(D)J platform. Single-cell suspensions were processed to generate paired gene expression and V(D)J libraries, with this dataset containing the V(D)J-enriched libraries targeting TCR α and β chains. Sequencing was performed on an Illumina platform to enable reconstruction of TCR clonotypes and analysis of clonal expansion. The dataset includes samples from patients with varying responses to immune checkpoint inhibitor therapy, supporting investigation of T cell clonality, antigen specificity, and immune dynamics associated with treatment response and resistance.	Illumina NovaSeq 6000	12