Liver tumour immune microenvironment subtypes and neutrophil heterogeneity
The heterogeneity of tumor immune microenvironment (TIME), organized by various immune and stromal cells, is a major cause of tumor metastasis and drug resistance, but how different TIME subtypes are connected to the clinical relevance in liver cancer remains elusive. Here, we performed single cell RNA-sequencing (scRNA-seq) on 189 samples collected from 124 patients and 8 mice with liver cancer. With over a million of cells analyzed, we stratified patients into five TIME subtypes including immune activation, suppression mediated by myeloid or by stromal cells, exclusion, and residence phenotypes. Different TIME subtypes appeared to be organized by specific cell populations, associated with chemokine networks and driver genes. Notably, within myeloid cell-enriched TIME subtype, tumor-associated neutrophil (TAN) populations, including one highly expressing macrophage-recruiting chemokines, CCL3 and CCL4, and another with high expression of the immune checkpoint CD274, were significantly associated with unfavorable prognosis. Both ex vivo analyses of patient neutrophils isolated from multiple tissue types and in vivo neutrophil depletion in mouse tumor models showed that TANs could recruit macrophages and suppress cytotoxicity of T cells. With this detailed cellular heterogeneity landscape of liver cancer, our study illustrates diverse TIME subtypes, highlights immunosuppressive functions of TANs, and sheds light on novel immunotherapies targeting TANs.
Select dataset and input interested genes
1. Load data
Note: please first select one or more dataset(s) to load. Wait until showing 'Done'.
2. Select dataset
3. Gene input
*,One gene per line and three genes one time are recommended.
Umap plot of select genes in the selected dataset
Vlnplot of genes in the selected dataset
Only when the dataset and genes were selected and submitted in the Embedding section, the plot of violin distribution will be shown
If you have done, please wait for seconds.
Markers of cell clusters
Dotheatmap of canonical cluster markers
Cluster distribution across samples
1. Select data
2. Group and plot
3. Result
Cluster distribution across samples
When the data was selected and plotted in the former Count section, the corresponding data table will be shown
DownloadSummary of TIMELASER
Including key cell subpopulation, marker genes, TIME-related signatures and prognosis.
Cytokine and interaction enriched in each TIMELASER subtype
About
This data portal is based on framework scDVA (short for single cell RNA-seq data visualization and analyzation).
This framework is developed by Qi Cao (caoqi2016@pku.edu.cn) of Ning Zhang's lab, Peking University.
Citation
Xue et al. Liver tumour immune microenvironment subtypes and neutrophil heterogeneity. Nature, 2022. https://www.nature.com/articles/s41586-022-05400-x
Contact us
For any questions about this data portal, please contact us: rxue@bjmu.edu.cn