Unveiling the role of PPIF and macrophage subtypes in LSCC progression via single-cell and exosome RNA sequencing

Laryngeal squamous cell carcinoma (LSCC) is a highly aggressive malignancy with a rising incidence over time. The tumor microenvironment (TME) plays a crucial role in LSCC development, yet the precise cellular characteristics of laryngeal cancer and its TME remain unclear. Here, we employed single-cell RNA sequencing analysis to uncover the heterogeneous populations of tumor and immune cells and investigate the role of the TME in LSCC. This analysis revealed significant heterogeneity among malignant cells, T cells, and macrophages. Notably, regulatory T cells were markedly increased at tumor sites, and macrophage analysis identified an increased presence of the Macrophage-C1-C1QC subset with up-regulated PPIF expression. Bulk RNA-seq further confirmed PPIF up-regulation in exosomes derived from LSCC tissues. Consistently, survival analysis indicated that high PPIF expression was associated with poor prognosis in LSCC. Further analyses suggested that PPIF up-regulation in Macrophage-C1-C1QC cells was associated with the enhancement of their anti-inflammatory phenotype and the promotion of F11R-F11R signaling with malignant cells, allowing LSCC cells to evade macrophage-mediated cytotoxicity. Our study provides new insights into the cellular dynamics of LSCC and highlights the critical role of Macrophage-C1-C1QC and PPIF in LSCC progression, offering potential therapeutic targets for treatment.