1. A distinct tumor microenvironment makes anaplastic thyroid cancer more lethal but immunotherapy sensitive than papillary thyroid cancer.
- Author
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Han PZ, Ye WD, Yu PC, Tan LC, Shi X, Chen XF, He C, Hu JQ, Wei WJ, Lu ZW, Qu N, Wang Y, Ji QH, Ji DM, and Wang YL
- Subjects
- Humans, Animals, Mice, Tertiary Lymphoid Structures immunology, Tertiary Lymphoid Structures pathology, Single-Cell Analysis, Prognosis, T-Lymphocytes immunology, Female, Immune Checkpoint Inhibitors therapeutic use, Immune Checkpoint Inhibitors pharmacology, Male, Tumor Microenvironment immunology, Thyroid Carcinoma, Anaplastic pathology, Thyroid Carcinoma, Anaplastic therapy, Thyroid Carcinoma, Anaplastic immunology, Thyroid Cancer, Papillary pathology, Thyroid Cancer, Papillary immunology, Thyroid Cancer, Papillary genetics, Thyroid Cancer, Papillary therapy, Thyroid Neoplasms pathology, Thyroid Neoplasms immunology, Thyroid Neoplasms therapy, Thyroid Neoplasms genetics, Immunotherapy methods, Chemokine CXCL13 metabolism, Chemokine CXCL13 genetics
- Abstract
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.
- Published
- 2024
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