Study on tumor ecology and precision medicine strategy of oral squamous cell carcinoma based on multi-omics cell atlas
- 1The First Affiliated Hospital of Wannan Medical University, Yijishan Hospital of Wannan Medical University
- 2College of Bioinformatics Science and Technology, Harbin Medical University
- 3The Second Affiliated Hospital of Harbin Medical University
Abstract
Introduction: 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.
Methods: We integrated single-cell RNA sequencing, single-cell T-cell receptor sequencing, spatial transcriptomics, and bulk RNA-sequencing data to characterize OSCC.
Results: 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.
Discussion: 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.
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BibTeX
@article{meng2026study,
title = {{Study on tumor ecology and precision medicine strategy of oral squamous cell carcinoma based on multi-omics cell atlas}},
author = {Qingkang Meng and Diwei Huo and Fei Xu and Naiqiang Liu and Muchen Fan and Yewen Wu and Xiujie Chen},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1925952},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1925952/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Study on tumor ecology and precision medicine strategy of oral squamous cell carcinoma based on multi-omics cell atlas
AU - Qingkang Meng
AU - Diwei Huo
AU - Fei Xu
AU - Naiqiang Liu
AU - Muchen Fan
AU - Yewen Wu
AU - Xiujie Chen
PY - 2026
DA - 2026/10/09
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1925952
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1925952/full
AB - Introduction: 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. Methods: We integrated single-cell RNA sequencing, single-cell T-cell receptor sequencing, spatial transcriptomics, and bulk RNA-sequencing data to characterize OSCC. Results: 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. Discussion: 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.
SN - 1664-3224
ER -