Single cell deciphering of progression trajectories of the tumor ecosystem in head and neck cancer.
Z L LiuX Y MengR J BaoM Y ShenJ J SunW D ChenF LiuYue HePublished in: Nature communications (2024)
Head and neck squamous cell carcinoma is the sixth most common cancer worldwide and has high heterogeneity and unsatisfactory outcomes. To better characterize the tumor progression trajectory, we perform single-cell RNA sequencing of normal tissue, precancerous tissue, early-stage, advanced-stage cancer tissue, lymph node, and recurrent tumors tissue samples. We identify the transcriptional development trajectory of malignant epithelial cells and a tumorigenic epithelial subcluster regulated by TFDP1. Furthermore, we find that the infiltration of POSTN + fibroblasts and SPP1 + macrophages gradually increases with tumor progression; their interaction or interaction with malignant cells also gradually increase to shape the desmoplastic microenvironment and reprogram malignant cells to promote tumor progression. Additionally, we demonstrate that during lymph node metastasis, exhausted CD8 + T cells with high CXCL13 expression strongly interact with tumor cells to acquire more aggressive phenotypes of extranodal expansion. Finally, we delineate the distinct features of malignant epithelial cells in primary and recurrent tumors, providing a theoretical foundation for the precise selection of targeted therapy for tumors at different stages. In summary, the current study offers a comprehensive landscape and deep insight into epithelial and microenvironmental reprogramming throughout initiation, progression, lymph node metastasis and recurrence of head and neck squamous cell carcinoma.
Keyphrases
- lymph node metastasis
- papillary thyroid
- single cell
- poor prognosis
- rna seq
- squamous cell carcinoma
- early stage
- lymph node
- induced apoptosis
- cell cycle arrest
- high throughput
- stem cells
- signaling pathway
- gene expression
- climate change
- long non coding rna
- squamous cell
- cell death
- adipose tissue
- metabolic syndrome
- sentinel lymph node
- neoadjuvant chemotherapy
- risk assessment
- transcription factor
- pi k akt
- insulin resistance