Distinct tumor microenvironment makes anaplastic thyroid cancer more lethal but immunotherapy-sensitive than papillary thyroid cancer

• DOI: 10.1172/jci.insight.173712
• Publication Date: 2024-03-13T17:24:28Z
• Authors: Pei-Zhen Han; Wei-Dong Ye; Peng-Cheng Yu; Li-Cheng Tan; Xiao Shi; Xu-Feng Chen; Cong He; Jia-Qian Hu; Wen-Jun Wei; Zhong-Wu Lu; Ning Qu; Yu Wang; Qing-Hai Ji; Dong-Mei Ji; Yu-Long Wang
• Keywords: Male; T-Lymphocytes; Thyroid Carcinoma, Anaplastic; Prognosis; Chemokine CXCL13; Mice; Tertiary Lymphoid Structures; Thyroid Cancer, Papillary; Tumor Microenvironment; Humans; Animals; Female; Thyroid Neoplasms; Immunotherapy; Single-Cell Analysis; Immune Checkpoint Inhibitors; Research Article

Both anaplastic thyroid cancer (ATC) and papillary thyroid cancer (PTC) originate from thyroid follicular epithelial cells, but ATC has a significantly worse prognosis and shows resistance to conventional therapies. However, clinical trials found that immunotherapy works better in ATC than late-stage PTC. Here, we used single-cell RNA sequencing (scRNA-Seq) to generate a single-cell atlas of thyroid cancer. Differences in ATC and PTC tumor microenvironment components (including malignant cells, stromal cells, and immune cells) leading to the polarized prognoses were identified. Intriguingly, we found that CXCL13+ T lymphocytes were enriched in ATC samples and might promote the development of early tertiary lymphoid structure (TLS). Last, murine experiments and scRNA-Seq analysis of a treated patient's tumor demonstrated that famitinib plus anti-PD-1 antibody could advance TLS in thyroid cancer. We displayed the cellular landscape of ATC and PTC, finding that CXCL13+ T cells and early TLS might make ATC more sensitive to immunotherapy.