Han Pei-Zhen, Ye Wei-Dong, Yu Peng-Cheng, Tan Li-Cheng, Shi Xiao, Chen Xu-Feng, He Cong, Hu Jia-Qian, Wei Wen-Jun, Lu Zhong-Wu, Qu Ning, Wang Yu, Ji Qing-Hai, Ji Dong-Mei, Wang Yu-Long
Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
JCI Insight. 2024 Mar 7;9(8):e173712. doi: 10.1172/jci.insight.173712.
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.
间变性甲状腺癌（ATC）和乳头状甲状腺癌（PTC）均起源于甲状腺滤泡上皮细胞，但ATC的预后明显更差，且对传统疗法表现出抗性。然而，临床试验发现免疫疗法在ATC中的效果优于晚期PTC。在此，我们使用单细胞RNA测序（scRNA-Seq）生成了甲状腺癌的单细胞图谱。我们确定了导致两极分化预后的ATC和PTC肿瘤微环境成分（包括恶性细胞、基质细胞和免疫细胞）的差异。有趣的是，我们发现CXCL13 + T淋巴细胞在ATC样本中富集，并且可能促进早期三级淋巴结构（TLS）的发育。最后，小鼠实验以及对一名接受治疗患者肿瘤的scRNA-Seq分析表明，法米替尼加抗PD-1抗体可促进甲状腺癌中的TLS。我们展示了ATC和PTC的细胞图谱，发现CXCL13 + T细胞和早期TLS可能使ATC对免疫疗法更敏感。
