MINI REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1651088
This article is part of the Research TopicExploring immune low-response states through single-cell technologies and spatial transcriptomicsView all 16 articles
Personalized immunotherapy strategies informed by single cell profiling in thyroid cancer: A mini review
Provisionally accepted
- 1Liaoning University of Traditional Chinese Medicine, Shenyang, China
- 2Department of endocrinology, The First Affiliated Hospital, Liaoning University of Traditional Chinese Medicine, Shenyang, China
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Thyroid cancer (TC) is now among the fastest-growing solid tumours, yet therapeutic gains remain limited for poorly differentiated, anaplastic and medullary variants whose median survivals are measured in months. Once guided chiefly by histology and single-gene assays, immunotherapy is being reshaped by single-cell profiling, which exposes the cellular mosaics that arbitrate response and resistance. Dissection of more than 150 000 tumour-and immune-cell transcriptomes has uncovered follicular-like, partial EMT-like and dedifferentiated thyrocyte states embedded within 'hot' (CD8 hi IFN-γ hi ), 'cold' (CD8 lo ) and 'excluded' (stroma-walled) immune niches; these phenotypes correlate with PD-1/LAG-3 expression, macrophage polarisation and radio-iodine refractoriness. Functional studies reveal that SPP1-CD44 and GAS6-AXL crosstalk licenses epithelial-mesenchymal transition while VSIG4⁺ macrophages blunt cytotoxic T-cell activity, collectively undermining checkpoint blockade. Spatial transcriptomics corroborates these insights, mapping PD-L1-high tumour islets millimetres from CXCL13-rich tertiary lymphoid structures, whereas CITE-seq quantifies actionable checkpoints and cytokine receptors across patient biopsies. Emerging therapeutics mirror this granular knowledge: combinatorial PD-1 + LAG-3 inhibition, CSF-1R-directed macrophage re-programming and TSH-receptor-targeted CAR-T cells are advancing through early-phase trials, while ex-vivo single-cell pharmacotyping aligns drug cocktails with an individual's tumour ecosystem. Early lenvatinib-pembrolizumab or selpercatinib-nivolumab trials show ~40 % ORR but grade-3 hypertension >60 %, prompting staggered-start designs. These advances sharpen pathogenetic resolution, refine patient selection and accelerate translational pipeline design. By integrating single-cell biology, immunology and endocrine oncology, this review identifies diagnostic blind spots, spotlights drug-repurposing opportunities and charts a roadmap toward personalised immunotherapeutic strategies capable of improving outcomes across the diverse spectrum of thyroid cancer.
Keywords: Single-cell RNA-sequencing, Spatial transcriptomics, tumour microenvironment, thyroid cancer, Immune checkpoint blockade, Macrophage reprogramming
Received: 20 Jun 2025; Accepted: 11 Aug 2025.
Copyright: © 2025 Chen, Wang, Chen, Huang, Zhang and Gao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Fengnuan Zhang, Department of endocrinology, The First Affiliated Hospital, Liaoning University of Traditional Chinese Medicine, Shenyang, China
Tianshu Gao, Department of endocrinology, The First Affiliated Hospital, Liaoning University of Traditional Chinese Medicine, Shenyang, China
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