GEO series
CAR-NKT cells induce low cytokine release syndrome by targeting hyperinflammatory macrophages with mitigation from GM-SCF inhibition.
GSE337190
Mus musculus
Expression profiling by high throughput sequencing
24 samples
Submitted 2026/08/07
Platform GPL24247
Summary
Chimeric antigen receptor (CAR)-T cell therapy has demonstrated remarkable efficacy in cancer treatment but is frequently limited by severe toxicities, including cytokine release syndrome (CRS), which is largely driven by host myeloid cell activation. CAR-engineered invariant natural killer T (CAR-NKT) cells have emerged as a promising alternative with comparable antitumor activity and reduced toxicity; however, the mechanisms underlying their improved safety profile remain poorly defined. Here, we systematically evaluate CRS induced by human CAR-NKT and CAR-T cells using a heavily tumor-bearing xenograft mouse model that recapitulates clinically relevant CRS. Compared with conventional CAR-T cells, CAR-NKT cells induce significantly lower CRS severity across multiple clinical and biochemical parameters. To elucidate the underlying mechanisms, we perform comprehensive single-cell transcriptomic profiling of mouse immune cells, including myeloid and granulocytic populations, across six anatomical compartments: tumor, blood, liver, lung, spleen, and bone marrow. This integrative analysis reveals dynamic immune remodeling during tumor progression, therapeutic intervention, and CRS development. Mechanistically, CAR-NKT cells preferentially target CD1d⁺ hyperinflammatory macrophages, a key driver of CRS, thereby limiting myeloid-mediated inflammatory responses. Furthermore, pharmacological inhibition of GM-CSF further attenuate CRS, supporting a combinatorial strategy to enhance the safety of CAR-NKT cell therapy. Collectively, these findings provide mechanistic insight into the reduced toxicity of CAR-NKT cells and support their development as a safer and effective platform for cancer immunotherapy.
This dataset
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Direct links to NCBI, no account and no request form: the whole study as GSE337190_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 24 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1484445 and SRA study SRP714241. Searching any of these in the dataset finder brings you back here.
Study design
24 conditions, each sampled once — no replicated groups
Read from 24 sample titles: 24 distinct titles with little repetition. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM9850163 Blank Peritoneal Fluid
- GSM9850164 Blank Blood
- GSM9850165 Blank Liver
- GSM9850166 Blank Lung
- GSM9850167 Blank Spleen
- GSM9850168 Blank Bone Marrow
- GSM9850169 Tumor Peritoneal Fluid
- GSM9850170 Tumor Blood
- GSM9850171 Tumor Liver
- GSM9850172 Tumor Lung
- GSM9850173 Tumor Spleen
- GSM9850174 Tumor Bone Marrow
- GSM9850175 T Peritoneal Fluid
- GSM9850176 T Blood
- GSM9850177 T Liver
- GSM9850178 T Lung
- GSM9850179 T Spleen
- GSM9850180 T Bone Marrow
- GSM9850181 NKT Peritoneal Fluid
- GSM9850182 NKT Blood
- GSM9850183 NKT Liver
- GSM9850184 NKT Lung
- GSM9850185 NKT Spleen
- GSM9850186 NKT Bone Marrow
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