GEO series
GABA promotes resistance to immunotherapy of patients with TLS-positive tumors [RNA-seq]
GSE273829
Homo sapiens
Expression profiling by high throughput sequencing
92 samples
Submitted 2026/07/08
Platform GPL24676
Summary
Tertiary lymphoid structures (TLS) correlate with favorable responses to immune checkpoint inhibitors (ICI) in various cancers, yet many patients with TLS-positive tumors are resistant to treatment. Multi-omic profiling of clear cell renal cell carcinoma (ccRCC) and soft tissue sarcoma tumors (STS) reveals an upregulation of gamma-aminobutyric acid (GABA)-related signatures in non-responders to ICI. In ccRCC, TLS from non-responders located near GABA-producing tumor cells, exhibit impaired B cell maturation, reduced IgG production, higher GABA receptor expression and tricarboxylic acid cycle activation. In vitro, exposure of human B cells to GABA reduces HLA-DR expression, proliferation and immunoglobulin secretion by receptor independent and dependent mechanisms. Pharmacological inhibition of GABA-synthesis increases ICI response and immune infiltration, particularly by B cells, in a TLS-positive STS mouse model. Our findings unravel GABA as an immunoregulatory metabolite and provide a rationale for its therapeutic targeting to overcome ICI resistance in patients with TLS-positive tumors.
This dataset
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Direct links to NCBI, no account and no request form: the whole study as GSE273829_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 92 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1143431 and SRA study SRP523884. Searching any of these in the dataset finder brings you back here.
Study design
36 conditions, each sampled once — no replicated groups
ccRCC tumor bulk RNA-seq ×4
ccRCC tumor bulk RNA-seq f ×2
Read from the first 40 of 92 sample titles: 36 distinct titles with little repetition. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM8437766 ccRCC tumor bulk RNA-seq b48c
- GSM8437767 ccRCC tumor bulk RNA-seq 919f
- GSM8437768 ccRCC tumor bulk RNA-seq f469
- GSM8437769 ccRCC tumor bulk RNA-seq 547f
- GSM8437770 ccRCC tumor bulk RNA-seq eba5
- GSM8437771 ccRCC tumor bulk RNA-seq e38f
- GSM8437772 ccRCC tumor bulk RNA-seq 816a
- GSM8437773 ccRCC tumor bulk RNA-seq 7216
- GSM8437774 ccRCC tumor bulk RNA-seq 764b
- GSM8437775 ccRCC tumor bulk RNA-seq 8523
- GSM8437776 ccRCC tumor bulk RNA-seq 743e
- GSM8437777 ccRCC tumor bulk RNA-seq 40ba
- GSM8437778 ccRCC tumor bulk RNA-seq bdd0
- GSM8437779 ccRCC tumor bulk RNA-seq 8c0e
- GSM8437780 ccRCC tumor bulk RNA-seq 8bbc
- GSM8437781 ccRCC tumor bulk RNA-seq 40de
- GSM8437782 ccRCC tumor bulk RNA-seq 0d38
- GSM8437783 ccRCC tumor bulk RNA-seq bc24
- GSM8437784 ccRCC tumor bulk RNA-seq caa3
- GSM8437785 ccRCC tumor bulk RNA-seq 3bea
- GSM8437786 ccRCC tumor bulk RNA-seq 44b3
- GSM8437787 ccRCC tumor bulk RNA-seq 0787
- GSM8437788 ccRCC tumor bulk RNA-seq 65f1
- GSM8437789 ccRCC tumor bulk RNA-seq 8831
- GSM8437790 ccRCC tumor bulk RNA-seq 4b33
- GSM8437791 ccRCC tumor bulk RNA-seq 61e8
- GSM8437792 ccRCC tumor bulk RNA-seq 19c0
- GSM8437793 ccRCC tumor bulk RNA-seq ccaf
- GSM8437794 ccRCC tumor bulk RNA-seq 579d
- GSM8437795 ccRCC tumor bulk RNA-seq ccbb
- GSM8437796 ccRCC tumor bulk RNA-seq 4f16
- GSM8437797 ccRCC tumor bulk RNA-seq f158
- GSM8437798 ccRCC tumor bulk RNA-seq e0c7
- GSM8437799 ccRCC tumor bulk RNA-seq 39c4
- GSM8437800 ccRCC tumor bulk RNA-seq d022
- GSM8437801 ccRCC tumor bulk RNA-seq 4a7b
- GSM8437802 ccRCC tumor bulk RNA-seq 3e11
- GSM8437803 ccRCC tumor bulk RNA-seq cff1
- GSM8437804 ccRCC tumor bulk RNA-seq eebb
- GSM8437805 ccRCC tumor bulk RNA-seq 5f65
+ 52 more — browse all 92 samples with per-sample file links →
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