Single-cell sequencing profiling of intratumoral heterogeneity and immunosuppressive microenvironment in primary thyroid cancer and lymph node metastases

作者：Shuhang Xu, Yaorong Su, Senmin Zhang, Dongye Huang, Song Wu, Cailu Song, Wenhuan Zhong, Lan Xie, Wenkuan Chen · 发表于：OncoImmunology · 年份：2026 · DOI：10.1080/2162402x.2026.2701504 · 研究领域：Thyroid Cancer Diagnosis and Treatment、Single-cell and spatial transcriptomics、Myasthenia Gravis and Thymoma

Metastasis is a major determinant of treatment failure and mortality in thyroid cancer, yet the interplay between malignant evolution and the immune microenvironment remains poorly characterized. Immunotherapy offers promise, but its efficacy requires a deeper understanding of tumor-associated immune infiltration and checkpoint regulation. In this study, we constructed a high-resolution transcriptomic atlas of the thyroid cancer ecosystem by analyzing 55,005 single cells from paired primary tumors and lymph node metastases. By integrating chromosomal copy number variation (CNV) inference with consensus nonnegative matrix factorization (cNMF), we deciphered the intrinsic heterogeneity of malignant epithelial cells, revealing distinct transcriptional programs and developmental trajectories driving the metastatic cascade. The metastatic niche exhibited significant reprogramming of the immunosuppressive landscape, characterized by the enrichment of FOXP3⁺ regulatory T (Treg) cells, LAMP3⁺ dendritic cells (DCs), and CCL18⁺ M2-like macrophages. Notably, while canonical checkpoints PD-1 and PD-L1/2 showed minimal expression, ligand-receptor interaction analysis identified the LAG3-LGALS3 axes as dominant immune evasion pathways mediating the crosstalk between CD8⁺ T cells and the tumor stroma. In conclusion, this study comprehensively maps the coevolution of malignant thyrocyte plasticity and the immunosuppressive metastatic niche. By uncovering the specific role of LAMP3⁺ DCs and i...