Hashimoto’s thyroiditis in differentiated thyroid cancer: autoimmune inflammation, immune surveillance, and tumor escape
- 1Department of Ultrasound, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China
- 2Department of Ultrasound, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China
Abstract
Hashimoto’s thyroiditis (HT) and differentiated thyroid cancer (DTC) frequently coexist, yet their biological relationship remains paradoxical. In this critical narrative review informed by a structured literature search, we synthesize epidemiological, clinicopathological, genomic, immunological, and translational evidence derived predominantly from papillary thyroid carcinoma (PTC) within the broader DTC framework to examine how HT may function as both a tumor-promoting inflammatory niche and a tumor-restraining immune microenvironment. In the proposed spear-and-shield model, chronic autoimmune inflammation may generate oxidative stress, cytokine signaling, and selective pressures that favor malignant transformation, whereas pre-existing lymphocytic infiltration, antigen presentation, B-cell organization, and cytotoxic T-cell activity may strengthen immune surveillance and contribute to favorable outcomes in selected patients. We further discuss how immune escape can emerge within an inflamed thyroid microenvironment through checkpoint activation, regulatory lymphocytes, myeloid polarization, dendritic-cell remodeling, and thyroid-stimulating hormone/thyroid-stimulating hormone receptor (TSH/TSHR)-related immune modulation. Finally, because most mechanistic and clinical evidence derives from papillary thyroid carcinoma, we emphasize that HT should be characterized according to its timing, histological features, antibody profile, thyroid functional status, and spatial immune organization. We propose that HT influences DTC through a stage- and genotype-dependent immune contexture rather than as a uniform risk factor, and identify testable biomarkers integrating T-cell and B-cell receptor clonality, tertiary lymphoid structure maturity, antigen presentation, checkpoint activation, thyroid differentiation, and TSH–TSHR signaling.
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BibTeX
@article{zhang2026hashimotos,
title = {{Hashimoto’s thyroiditis in differentiated thyroid cancer: autoimmune inflammation, immune surveillance, and tumor escape}},
author = {Zijian Zhang and Likun Cui and Quan Dai and Chuanshi He and Li Han and Min Zhuang and Lu Wang and Ziyue Hu and Xiaoxiao Xie and Yuping Shen and Jinshun Xu and Man Lu},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1945791},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1945791/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Hashimoto’s thyroiditis in differentiated thyroid cancer: autoimmune inflammation, immune surveillance, and tumor escape
AU - Zijian Zhang
AU - Likun Cui
AU - Quan Dai
AU - Chuanshi He
AU - Li Han
AU - Min Zhuang
AU - Lu Wang
AU - Ziyue Hu
AU - Xiaoxiao Xie
AU - Yuping Shen
AU - Jinshun Xu
AU - Man Lu
PY - 2026
DA - 2026/10/16
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1945791
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1945791/full
AB - Hashimoto’s thyroiditis (HT) and differentiated thyroid cancer (DTC) frequently coexist, yet their biological relationship remains paradoxical. In this critical narrative review informed by a structured literature search, we synthesize epidemiological, clinicopathological, genomic, immunological, and translational evidence derived predominantly from papillary thyroid carcinoma (PTC) within the broader DTC framework to examine how HT may function as both a tumor-promoting inflammatory niche and a tumor-restraining immune microenvironment. In the proposed spear-and-shield model, chronic autoimmune inflammation may generate oxidative stress, cytokine signaling, and selective pressures that favor malignant transformation, whereas pre-existing lymphocytic infiltration, antigen presentation, B-cell organization, and cytotoxic T-cell activity may strengthen immune surveillance and contribute to favorable outcomes in selected patients. We further discuss how immune escape can emerge within an inflamed thyroid microenvironment through checkpoint activation, regulatory lymphocytes, myeloid polarization, dendritic-cell remodeling, and thyroid-stimulating hormone/thyroid-stimulating hormone receptor (TSH/TSHR)-related immune modulation. Finally, because most mechanistic and clinical evidence derives from papillary thyroid carcinoma, we emphasize that HT should be characterized according to its timing, histological features, antibody profile, thyroid functional status, and spatial immune organization. We propose that HT influences DTC through a stage- and genotype-dependent immune contexture rather than as a uniform risk factor, and identify testable biomarkers integrating T-cell and B-cell receptor clonality, tertiary lymphoid structure maturity, antigen presentation, checkpoint activation, thyroid differentiation, and TSH–TSHR signaling.
SN - 1664-3224
ER -