Related Experiment Video
Updated: Aug 18, 2025
Establishment of Gastric Cancer Patient-derived Xenograft Models and Primary Cell Lines
Published on: July 19, 2019
Reconstruction of the gastric cancer microenvironment after neoadjuvant chemotherapy by longitudinal single-cell
Yingtai Chen1, Jianhua Yin2,3,4, Lulu Zhao1
1National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli, Beijing, 100021, China.
Background:
Little is known on the tumor microenvironment (TME) response after neoadjuvant chemotherapy (NACT) in gastric cancer on the molecular level.
Methods:
Here, we profiled 33,589 cell transcriptomes in 14 samples from 11 gastric cancer patients (4 pre-treatment samples, 4 post-treatment samples and 3 pre-post pairs) using single-cell RNA sequencing (scRNA-seq) to generate the cell atlas. The ligand-receptor-based intercellular communication networks of the single cells were also characterized before and after NACT.
Results:
Compered to pre-treatment samples, CD4+ T cells (P = 0.018) and CD8+ T cells (P = 0.010) of post-treatment samples were significantly decreased, while endothelial cells and fibroblasts were increased (P = 0.034 and P = 0.005, respectively). No significant difference observed with respect to CD4+ Tregs cells, cycling T cells, B cells, plasma cells, macrophages, monocytes, dendritic cells, and mast cells (P > 0.05). In the unsupervised nonnegative matrix factorization (NMF) analysis, we revealed that there were three transcriptional programs (NMF1, NMF2 and NMF3) shared among these samples. Compared to pre-treatment samples, signature score of NMF1 was significantly downregulated after treatment (P = 0.009), while the NMF2 signature was significantly upregulated after treatment (P = 0.013). The downregulated NMF1 and upregulated NMF2 signatures were both associated with improved overall survival outcomes based on The Cancer Genome Atlas (TCGA) database. Additionally, proangiogenic pathways were activated in tumor and endothelial cells after treatment, indicating that NACT triggers vascular remodeling by cancer cells together with stromal cells.
Conclusions:
In conclusion, our study provided transcriptional profiles of TME between pre-treatment and post-treatment for in-depth understanding on the mechanisms of NACT in gastric cancer and empowering the development of potential optimized therapy procedures and novel drugs.
Insights
Neoadjuvant chemotherapy (NACT) alters the gastric cancer tumor microenvironment (TME). Post-treatment, T cells decrease while endothelial cells and fibroblasts increase, impacting survival outcomes and suggesting vascular remodeling.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- The tumor microenvironment (TME) response to neoadjuvant chemotherapy (NACT) in gastric cancer remains poorly understood at the molecular level.
- Gastric cancer treatment strategies require deeper insights into TME dynamics.
Purpose of the Study:
- To characterize the molecular changes in the gastric cancer TME after NACT.
- To identify cellular and molecular alterations associated with NACT response and patient survival.
Main Methods:
- Single-cell RNA sequencing (scRNA-seq) was employed to profile 33,589 cell transcriptomes from 11 gastric cancer patients (pre- and post-NACT).
- Ligand-receptor-based intercellular communication networks were analyzed.
- Nonnegative matrix factorization (NMF) was used to identify shared transcriptional programs.
Main Results:
- Post-NACT samples showed significant decreases in CD4+ and CD8+ T cells, and increases in endothelial cells and fibroblasts.
- Three shared transcriptional programs (NMF1, NMF2, NMF3) were identified; NMF1 decreased and NMF2 increased post-NACT.
- Downregulated NMF1 and upregulated NMF2 signatures correlated with improved overall survival (TCGA data).
- Proangiogenic pathways were activated post-NACT, indicating NACT-induced vascular remodeling.
Conclusions:
- This study provides comprehensive transcriptional profiles of the gastric cancer TME before and after NACT.
- Findings elucidate NACT mechanisms and support the development of optimized therapies and novel drugs for gastric cancer.
