A distinct tumor microenvironment makes anaplastic thyroid cancer more lethal but immunotherapy sensitive than papillary thyroid cancer

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.

Keywords: Immunotherapy; Oncology; Thyroid disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chemokine CXCL13* / genetics
  • Chemokine CXCL13* / metabolism
  • Female
  • Humans
  • Immune Checkpoint Inhibitors / pharmacology
  • Immune Checkpoint Inhibitors / therapeutic use
  • Immunotherapy* / methods
  • Male
  • Mice
  • Prognosis
  • Single-Cell Analysis
  • T-Lymphocytes / immunology
  • Tertiary Lymphoid Structures / immunology
  • Tertiary Lymphoid Structures / pathology
  • Thyroid Cancer, Papillary* / genetics
  • Thyroid Cancer, Papillary* / immunology
  • Thyroid Cancer, Papillary* / pathology
  • Thyroid Cancer, Papillary* / therapy
  • Thyroid Carcinoma, Anaplastic* / immunology
  • Thyroid Carcinoma, Anaplastic* / pathology
  • Thyroid Carcinoma, Anaplastic* / therapy
  • Thyroid Neoplasms* / genetics
  • Thyroid Neoplasms* / immunology
  • Thyroid Neoplasms* / pathology
  • Thyroid Neoplasms* / therapy
  • Tumor Microenvironment* / immunology


  • Chemokine CXCL13
  • CXCL13 protein, human
  • Immune Checkpoint Inhibitors