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Visualization, Quantification, and Mapping of Immune Cell Populations in the Tumor Microenvironment
Published on: March 25, 2020
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Tumor microenvironment remodeling across thyroid cancer differentiation states revealed by spatial transcriptomics
Jungirl Seok1,2, Hongyoon Choi3,4, Eun Kyung Lee5
1Department of Otorhinolaryngology-Head and Neck Surgery, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 10408, Republic of Korea.
Cancer Immunology, Immunotherapy : CII
|November 3, 2025
Summary
Thyroid cancer dedifferentiation creates an immunosuppressive tumor microenvironment (TME) promoting aggressive growth. Targeting JAK-STAT and VEGF pathways or boosting natural killer (NK) cells may treat advanced thyroid cancers.
Area of Science:
- Oncology
- Immunology
- Genomics
Background:
- Thyroid cancer is the most common endocrine malignancy, with increasing incidence.
- Differentiated thyroid cancers (DTC) have good prognoses, unlike aggressive poorly differentiated (PDTC) and anaplastic (ATC) types.
- Understanding the tumor microenvironment (TME) is key for new thyroid cancer therapies.
Purpose of the Study:
- To investigate the tumor microenvironment (TME) in thyroid cancer dedifferentiation using spatial transcriptomics.
- To identify cellular and molecular changes associated with aggressive thyroid cancer subtypes.
Main Methods:
- Spatial transcriptomics (ST) on 12 thyroid tumor tissues (PTC, FTC, PDTC, ATC).
- Cell type composition inferred with CellDART; pathway activity assessed via PROGENy and REACTOME.
- Immunohistochemistry (IHC) used for validating TME components.
Main Results:
- Dedifferentiation correlated with increased myeloid cells and cancer-associated fibroblasts (CAFs), and decreased NK cells and endothelial cells.
- Myeloid-derived suppressor cell (MDSC) scores negatively correlated with thyroid differentiation.
- Upregulated JAK-STAT and VEGF signaling pathways in dedifferentiated tumors linked to myeloid cell infiltration.
Conclusions:
- Thyroid cancer dedifferentiation is linked to an immunosuppressive TME that drives tumor progression.
- Targeting JAK-STAT, VEGF, or enhancing NK cell activity are potential therapeutic strategies for aggressive thyroid cancers.
- Larger studies are needed to validate findings and develop targeted therapies.
