Dissecting Concurrent Chemoradiotherapy-Induced Landscape Alteration of Tumor Microenvironment in Locally Advanced Cervical Cancer at Single Cell Resolution.

Purpose/Objective(s) We previously identified changes of immune cells in the cervical cancer microenvironment following concurrent chemoradiotherapy (CCRT) at single cell resolution. However, changes of other cells in the tumor microenvironment are unknown; thus, we further investigated CCRT-induced landscape alteration of all cells in the tumor microenvironment of locally advanced cervical cancer (LACC) using single-cell RNA sequencing. Materials/Methods We performed single-cell RNA sequencing of 5 paired of tumor biopsies before and during CCRT in LACC patients and identified the subsets of epithelial cells, cancer-associated fibroblasts, immune cells, and endothelial cells and their alterations following CCRT. We also used immunostaining to validate our findings. Results Seven clusters of epithelial cells, 2 clusters of mCAF and 7 clusters of vCAF, 7 clusters of myeloid cells, 10 clusters of T cells and 2 clusters of NK cells, and 3 clusters of endothelial cells were identified in cervical cancer. Epithelial cells, mCAF and myeloid cells dramatic changed following CCRT. The proportion of a highly proliferate cluster of epithelial cells was decreased induced by CCRT, while a pre-malignant cluster of epithelial cells was predominant during CCRT. CCRT induced the transition of mCAF from one subset to another. For T cells, CCL5+CD8+ T cells, exhausted CD8+ T cells, and proliferate T cells were predominant before CCRT, but not during CCRT; cytotoxic CD8+ T cells were mainly existed in the tumor environment during CCRT. Conclusion Our work reveals the landscape alteration of tumor microenvironment induced by CCRT in LACC patients at single-cell resolution.