Our study uses single-cell RNA sequencing and spatial transcriptome sequencing to examine the cell dynamics in RC patients before and after treatment. We find that NAC remodels the populations of cancer-associated fibroblasts, leading to improved therapeutic response and inhibition of tumor progression through modulation of the tumor microenvironment.
Neoadjuvant chemotherapy (NAC) for rectal cancer (RC) shows promising clinical response. The modulation of the tumor microenvironment (TME) by NAC and its association with therapeutic response remain unclear. Here, we use single-cell RNA sequencing and spatial transcriptome sequencing to examine the cell dynamics in 29 patients with RC, who are sampled pairwise before and after treatment. We construct a high-resolution cellular dynamic landscape remodeled by NAC and their associations with therapeutic response. NAC mark-edly reshapes the populations of cancer-associated fibroblasts (CAFs), which is strongly associated with therapeutic response. The remodeled CAF subsets regulate the TME through spatial recruitment and cross-talk to activate immunity and suppress tumor progression through multiple cytokines, including CXCL12, SLIT2, and DCN. In contrast, the epithelial-mesenchymal transition of malignant cells is upregulated by CAF_FAP through MIR4435-2HG induction, resulting in worse outcomes. Our study demonstrates that NAC inhibits tumor progression and modulates the TME by remodeling CAFs.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据