Study on tumor ecology and precision medicine strategy of oral squamous cell carcinoma based on multi-omics cell...

Oral squamous cell carcinoma (OSCC) is characterized by inter- and intratumoral heterogeneity, which complicates patient stratification and treatment. Although single-cell studies have improved the resolution of the OSCC microenvironment, the relationships among cellular states, spatial organization, immune-repertoire dynamics, and patient-level ecosystem patterns remain incompletely understood.

We integrated single-cell RNA sequencing, single-cell T-cell receptor sequencing, spatial transcriptomics, and bulk RNA-sequencing data to characterize OSCC.

We constructed a multi-omics cellular atlas comprising 88,442 cells and 63 cell subclusters, revealing complementary malignant-cell heterogeneity at the levels of transcriptional subclusters and recurrent meta-programs. Spatial and cell-cell communication analysis identified a reproducible association between PI3+ cancer-associated fibroblasts and APC_Myeloid cells and supported a candidate collagen-associated communication axis within tumor niches. Integration of paired transcriptomic and TCR data delineated a CD8+ T-cell pseudotime continuum accompanied by increasing clonal expansion and exhaustion-associated features, with spatial analysis linking intermediate trajectory states to regulatory T-cell and inflammatory NKT-cell-rich tumor-front regions. Extending the single-cell atlas to bulk cohorts by deconvolution, we defined four OSCC ecotypes and four coordinated cell programs that captured patient-level ecosystem organization and showed distinct molecular and clinical associations. We developed exploratory models for prognosis, recurrence, and immunotherapy sensitivity and established the OSCC Atlas as an online resource for data exploration.

This integrative framework links cellular heterogeneity, spatial organization, immune dynamics, and patient-level ecology, providing testable hypotheses for the biological and clinical stratification of OSCC.