GEO series

Tumor-derived kynurenine induces Siglec-15 expression and promotes CD8+T cell exhaustion in oral squamous cell carcinoma

GSE222673 Homo sapiens (human) RNA-seq (gene expression) 138 samples Submitted 2024/07/03 Platform GPL20795

At a glance

RNA-seq (gene expression) · human · 138 samples

What it is: RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism: Homo sapiens (human)
Topic: Head and neck cancerThis series is part of our curated briefing on it.
Samples: 138 samples: 69 × N vs 69 × TGroups are read from the sample names, not from the paper. Check the list below.
Data you can get: A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper: Metabolic landscape of head and neck squamous cell carcinoma informs a novel kynurenine/Siglec-15 axis in immune escapeCancer communications (London, England) · 2024

Summary (written by the submitters)

Metabolic deregulation and immune escape are pivotal hallmarks of cancer; however, the profile of metabolic reprogramming in oral squamous cell carcinoma (OSCC) and how it drives immune escape remain unclear. We identified significant metabolic disorders in OSCC. Amino acid metabolism, especially tryptophan/kynurenine metabolism, was altered.

Read the full summary ↓

Here, we found that kynurenine promotes migration, invasion, and proliferation in vitro and in vivo. In addition, most immune checkpoints were upregulated in patients with high kynurenine levels. We then identified that kynurenine can promote Siglec-15 expression via AhR activation. Furthermore, tumor-derived kynurenine can directly exhaust CD8+ T cells, whereas blocking of kynurenine transporters reversed this effect. Moreover, we found that ectopic expression of Siglec-15 can promote immune escape in tumor microenvironment (TME) by suppressing T cell infiltration and inducing CD8+ T cell exhaustion in vivo, while targeting AhR reduces kynurenine-mediated immune escape. Finally, we design NH2-MSNs nanoparticles to deliver Siglec-15 small interfering RNA, which successfully remodels the TME and enhances anti-PD-1 efficacy in tumor-bearing immunocompetent mice. Clinically, Siglec-15 expression is correlated with AhR expression and high infiltration of exhausted CD8+ T cells. These findings reveal that the Kyn/AhR/Siglec-15 signaling pathway is a novel immunometabolism mechanism in OSCC, thus opening a new therapeutic avenue for metabolic immunotherapy.

Published in

Metabolic landscape of head and neck squamous cell carcinoma informs a novel kynurenine/Siglec-15 axis in immune escape

Zhang XY, Shi JB, Jin SF et al. · Cancer communications (London, England) 2024 · PMID 38734931 · doi:10.1002/cac2.12545

This dataset

Open GSE222673 in finder → Find more human RNA-seq datasets → Head and neck cancer landscape →

Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE222673_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓

3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA923002 and SRA study SRP417068. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 38734931) ↗

Study design

69 × N vs 69 × T

Supports a between-group comparison across 138 samples.

How we read this: 2 replicated groups read from 138 sample titles; they account for 138 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study

GSM6928669 N1 N
GSM6928670 N10 N
GSM6928671 N11 N
GSM6928672 N12 N
GSM6928673 N13 N
GSM6928674 N14 N
GSM6928675 N15 N
GSM6928676 N16 N
GSM6928677 N17 N
GSM6928678 N18 N
GSM6928679 N19 N
GSM6928680 N2 N
GSM6928681 N20 N
GSM6928682 N21 N
GSM6928683 N22 N
GSM6928684 N23 N
GSM6928685 N24 N
GSM6928686 N25 N
GSM6928687 N26 N
GSM6928688 N27 N
GSM6928689 N28 N
GSM6928690 N29 N
GSM6928691 N3 N
GSM6928692 N30 N
GSM6928693 N31 N
GSM6928694 N32 N
GSM6928695 N33 N
GSM6928696 N34 N
GSM6928697 N35 N
GSM6928698 N36 N
GSM6928699 N37 N
GSM6928700 N38 N
GSM6928701 N39 N
GSM6928702 N4 N
GSM6928703 N40 N
GSM6928704 N41 N
GSM6928705 N42 N
GSM6928706 N43 N
GSM6928707 N44 N
GSM6928708 N45 N

+ 98 more — browse all 138 samples with per-sample file links →

More Head and neck cancer datasets

GSE140042 Single-cell atlas of head and neck squamous cell carcinoma 18 samples same disease briefing · shares squamous
GSE185965 Single cell RNA sequencing of head and neck squamous carcinoma (HNSCC) patient sample 3 samples same disease briefing · shares squamous
GSE173647 Single-cell Sequencing Analysis of Head and Neck Squamous Cell Carcinoma 2 samples same disease briefing · shares squamous
GSE176077 RNA-seq profiling of salivary transcriptome reveals potential diagnostic RNAs and oral microbial dysbiosis in oral squamous cell carcinoma 28 samples same disease briefing · shares squamous
GSE103322 Single cell RNA-seq analysis of head and neck cancer 5901 samples same disease briefing
GSE139324 Immune landscape of viral- and carcinogen-drived head and neck cancer 63 samples same disease briefing
GSE162738 Immune gene signatures in oropharyngeal cancers are associated with inverse prognosis by HPV-status 51 samples same disease briefing
GSE164690 Investigating Immune and Non-Immune Cell Interactions in Head and Neck Tumors by Single-Cell RNA Sequencing 51 samples same disease briefing

Search all human RNA-seq datasets in GEO →

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Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.