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Single-cell transcriptome analysis revealed the immune profile of PD-1 blockade in gallbladder carcinoma liver
Lin Xie1,2, Zhouyu Ning1,2, Yongqiang Hua1,2
1Department of Minimally Invasive Therapy Center, Fudan University Shanghai Cancer Center, Shanghai, P. R. China.
Background:
Gallbladder carcinoma is the most common cancer of the biliary tract, and the immune checkpoint blockade showed promising efficacy in the treatment of advanced gallbladder carcinoma. However, the underlying mechanisms remain unknown.
Methods:
Single-cell RNA sequencing was used to reveal immune cell dynamics in an anti-PD-1 responder with gallbladder carcinoma liver metastases. Gene set variation analysis, pseudotime analysis, single-cell regulatory network inference and clustering analysis, and CellChat analysis were used to identify the functions of each cell cluster. Immunohistochemistry and multicolored immunohistochemistry analysis were applied to confirm the intratumoral cell types, and the prognostic value of CXCL13+CD8+T cells in patients with gallbladder carcinoma liver metastases with immunotherapy was evaluated. Four biliary tract carcinoma and 3 immunotherapy bulk RNA-seq datasets were analyzed to investigate the prognostic value of CXCL13+CD8+T cells and SPP1+TAMs.
Result:
A total of 19,648 high-quality single-cell transcriptome data were obtained from liver metastasis before and after aPD-1 therapy. We discovered improved cytotoxic activity in CD8+T cells and enhanced proinflammatory phenotypes in myeloid cells. The identified SPP1+TAMs were related to poor prognosis. The increased effector/memory T cells represented characteristics similar to exhausted T cells in transitory status after aPD-1therapy, which may play a crucial role in the antitumor immune response. We further revealed that CXCL13+T cells in a high subtype of biliary tract carcinoma were characterized as a 'hot tumor' profile with high immune scores, correlated to the immunostimulatory context with favorable survival, and can predict effective responses to immunotherapy.
Conclusions:
Our study provided an overview of immune cell dynamics in gallbladder carcinoma liver metastases after aPD-1 treatment and highlighted the importance of CXCL13+T cells in biliary tract carcinoma and effective responses to immunotherapy, which would advance the understanding and treatment of the disease.
Insights
Immune cell dynamics in gallbladder carcinoma liver metastases were analyzed after anti-PD-1 therapy. CXCL13+T cells show potential as a biomarker for predicting immunotherapy response in biliary tract cancers.
Area of Science:
- Immunology
- Oncology
- Genomics
Background:
- Gallbladder carcinoma is a common biliary tract cancer.
- Immune checkpoint blockade shows promise for advanced gallbladder carcinoma.
- Underlying mechanisms of treatment response remain unclear.
Purpose of the Study:
- To investigate immune cell dynamics in gallbladder carcinoma liver metastases after anti-PD-1 therapy.
- To identify key immune cell populations and their functions.
- To evaluate the prognostic value of specific immune cells in immunotherapy response.
Main Methods:
- Single-cell RNA sequencing of liver metastases before and after anti-PD-1 therapy.
- Bioinformatic analyses including gene set variation, pseudotime, and network inference.
- Immunohistochemistry to confirm cell types and assess prognostic value.
- Analysis of bulk RNA-seq datasets to validate findings.
Main Results:
- Enhanced cytotoxic activity in CD8+T cells and pro-inflammatory myeloid cells observed post-therapy.
- SPP1+ TAMs associated with poor prognosis.
- Increased effector/memory T cells showed characteristics of exhausted T cells.
- CXCL13+ T cells identified as a 'hot tumor' profile in a biliary tract carcinoma subtype, correlating with favorable survival and predicting immunotherapy response.
Conclusions:
- The study elucidates immune cell dynamics following anti-PD-1 treatment in gallbladder carcinoma liver metastases.
- CXCL13+ T cells are highlighted for their importance in biliary tract carcinoma and predicting immunotherapy response.
- Findings advance understanding and potential treatment strategies for gallbladder carcinoma.
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