Single-cell transcriptomic analyses reveal heterogeneity and key subsets associated with survival and response to PD-1 blockade in cervical squamous cell carcinoma

Abstract Understanding the intricate tumor microenvironment (TME) is crucial for elucidating the mechanisms underlying the progression of cervical squamous cell carcinoma (CSCC) and its response to anti-PD-1 therapy. In this study, we characterized 50,649 cells obtained from CSCC for single-cell RNA sequencing and integrated bulk sequencing data from The Cancer Genome Atlas (TCGA) and clinical specimens to explore cell composition, metabolic processes, signaling pathways, specific transcription factors, lineage tracking and response to immunotherapy. We identified 31 subsets of stromal and immune cells in the tumor microenvironment (TME) and observed distinct patterns in the metabolic processes and signaling pathways of these cells between tumor and normal tissues. Collagen signaling was found to be crucial for the interaction between stromal and immune cells. Furthermore, PCLAF-TAEpis were negatively correlated with CXCL13+CD8+ tumor-reactive T cells, overall survival, and the response to anti-PD-1therapy in patients with CSCC. In vivo experiments demonstrated that PCLAF-TAEpis promoted tumor growth and hindered the therapeutic efficacy of anti-PD-1 treatment by inhibiting the infiltration and function of T cells. Collectively, our findings illuminate the heterogeneity of the complex TME in CSCC and offer evidence supporting PCLAF-TAEpis as a promising therapeutic target.