Reconstruction of the gastric cancer microenvironment after neoadjuvant chemotherapy by longitudinal single-cell sequencing

• DOI: 10.1186/s12967-022-03792-y
• Publication Date: 2022-12-06T08:04:04Z
• Authors: Yingtai Chen; Jianhua Yin; Lulu Zhao; Guangyu Zhou; Shichen Dong; Yueming Zhang; Penghui Niu; Hu Ren; Tianjiao Zheng; Juan Yan; Wenbin Li; Peiqin Ma; Cuijuan Zhang; Chen Wei; George Church; Guibo Li; Dongbing Zhao
• Keywords: CD163

Abstract Background Little is known on the tumor microenvironment (TME) response after neoadjuvant chemotherapy (NACT) in gastric cancer molecular level. Methods Here, we profiled 33,589 cell transcriptomes 14 samples from 11 patients (4 pre-treatment samples, 4 post-treatment and 3 pre-post pairs) using single-cell RNA sequencing (scRNA-seq) to generate atlas. The ligand-receptor-based intercellular communication networks of single cells were also characterized before NACT. Results Compered CD4+ T (P = 0.018) CD8+ 0.010) significantly decreased, while endothelial fibroblasts increased 0.034 P 0.005, respectively). No significant difference observed with respect Tregs cells, cycling B plasma macrophages, monocytes, dendritic mast > 0.05). In unsupervised nonnegative matrix factorization (NMF) analysis, revealed that there three transcriptional programs (NMF1, NMF2 NMF3) shared among these samples. Compared signature score NMF1 was downregulated treatment 0.009), upregulated 0.013). signatures both associated improved overall survival outcomes based Cancer Genome Atlas (TCGA) database. Additionally, proangiogenic pathways activated treatment, indicating NACT triggers vascular remodeling by together stromal cells. Conclusions conclusion, our study provided profiles TME between for in-depth understanding mechanisms empowering development potential optimized therapy procedures novel drugs.