Thyroid autoimmune disorders and cancer

Ferrari, Silvia; Fallahi, Poupak; Elia, Giusy; Ragusa, Francesca; Ruffilli, Ilaria; Paparo, Sabrina Rosaria; Antonelli, Alessandro

doi:10.1016/j.semcancer.2019.05.019

Cited by 112 publications

(108 citation statements)

References 182 publications

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“…Therefore, to evaluate the speci c pattern of immune cells involved in PTC, including not only its phenotype but also its function, it is essential to understand the immunological characteristics of PTC. Many major advances have been made in the study of immune in ltration in PTC, especially in major immune cells (B cells, TAMs, NK cells, neutrophils, DCs, MCs, CD8 + T cells and Tregs) [13][14][15]. A considerable part of our research is repeating, verifying, and integrating previously reported results of immune cell phenotypes and functions in PTC.…”

Section: Discussionsupporting

confidence: 76%

“…2G). The construction of the balance chart mainly refers to the reviews by Varricchi et al [13], Galdiero et al [14] and Ferrari et al [15] and the literature table we made (Table 1).…”

Section: Increased Proportion Of Tumor-promoting Immune Cells In Ptcmentioning

confidence: 99%

“…Existing evidence shows that Tregs, neutrophils, dendritic cells (DCs), MCs, and TAMs play a tumorigenic role in the PTC tumor microenvironment (TME), while CD8 + T cells, B cells, and NK cells play a protective role [13][14][15]. However, the in ltration and role of some major immune cells in PTC are still controversial.…”

Section: Introductionmentioning

confidence: 99%

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Immune cell confrontation in the papillary thyroid carcinoma microenvironment

Xie

et al. 2020

Preprint

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Background Papillary thyroid carcinoma (PTC) is classified as an inflammation-driven cancer. A systematic understanding of immune cell infiltration in PTC is essential for subsequent immune research and new diagnostic and therapeutic strategies. Methods Three different algorithms, single-sample gene set enrichment analysis (ssGSEA), immune cell marker and CIBERSORT, were used to evaluate the immune cell infiltration levels (abundance and proportion) in 10 data sets (The Cancer Genome Atlas [TCGA], GSE3467, GSE3678, GSE5364, GSE27155, GSE33630, GSE50901, GSE53157, GSE58545, and GSE60542; a total of 799 PTC and 194 normal thyroid samples). Consensus unsupervised clustering divided PTC patients into low-immunity and high-immunity groups. Weighted gene coexpression network analysis (WGCNA) and gene set enrichment analysis (GSEA) were used to analyze the potential mechanisms that cause differences in the immune response. Results Compared with normal tissues, PTC tissues had a higher overall immune level, and the M2 macrophages, Tregs, monocytes, neutrophils, dendritic cells (DCs), mast cells (MCs), and M0 macrophages had higher abundances and proportions in PTC tissues. Compared with early PTC, advanced PTC had higher immune infiltration, and M2 macrophages, Tregs, monocytes, neutrophils, DCs, MCs, and M0 macrophages had higher abundances and proportions in advanced PTC. Compared to the low-immunity group patients, the high-immunity group patients presented with a more advanced stage, a larger tumor size, greater lymph node metastasis, higher tall-cell PTC, lower follicular PTC proportions, more BRAF mutations and fewer RAS mutations. Epstein-Barr virus (EBV) infection was the most significantly enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway for key module genes. Conclusions In human PTC, M2 macrophages, Tregs, monocytes, neutrophils, DCs, MCs, and M0 macrophages played a tumor-promoting role, while M1 macrophages, CD8 + T cells, B cells, NK cells, and T follicular helper (TFH) cells (including eosinophils, γδ T cells, and Th17 cells, with weak supporting evidence) played an antitumor role. During the occurrence and development of PTC, the overall immune level was increased, and the abundance and proportion of tumor-promoting immune cells were significantly increased, indicating that immune escape had aggravated. Finally, we speculate that EBV may play an important role in changing the immune microenvironment of PTC tumors.

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Section: Discussionsupporting

confidence: 76%

“…2G). The construction of the balance chart mainly refers to the reviews by Varricchi et al [13], Galdiero et al [14] and Ferrari et al [15] and the literature table we made (Table 1).…”

Section: Increased Proportion Of Tumor-promoting Immune Cells In Ptcmentioning

confidence: 99%

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Immune cell confrontation in the papillary thyroid carcinoma microenvironment

Xie

et al. 2020

Preprint

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“…A systematic review on studies, carried out in their majority on Caucasian populations, reported that incidence of hypothyroidism, which is commonly associated with HT, is 350/100,000/year in women and 80/100,000/year in men [8]. Although controversial discussed, several studies including a meta-analysis on fine-needle aspiration (FNA) and thyroidectomy studies reported HT as a risk factor for papillary thyroid carcinoma (PTC) development, and this observation was mainly based on the proportionally higher incidence of PTC with (w/) HT compared to PTC without (w/o) HT [9,10].…”

Section: Introductionmentioning

confidence: 99%

Genetic relationship between Hashimoto`s thyroiditis and papillary thyroid carcinoma with coexisting Hashimoto`s thyroiditis

et al. 2020

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Hashimoto's thyroiditis (HT) is present in the background of around 30% of papillary thyroid carcinomas (PTCs). The genetic predisposition effect of this autoimmune condition is not thoroughly understood. We analyzed the microarray expression profiles of 13 HT, eight PTCs with (w/) coexisting HT, six PTCs without (w/o) coexisting HT, six micro PTCs (mPTCs), and three normal thyroid (TN) samples. Based on a false discovery rate (FDR)adjusted p-value � 0.05 and a fold change (FC) > 2, four comparison groups were defined, which were HT vs. TN; PTC w/ HT vs. TN; PTC w/o HT vs. TN; and mPTC vs. TN. A Venn diagram displayed 15 different intersecting and non-intersecting differentially expressed gene (DEG) sets, of which a set of 71 DEGs, shared between the two comparison groups HT vs. TN \ PTC w/ HT vs. TN, harbored the relatively largest number of genes related to immune and inflammatory functions; oxidative stress and reactive oxygen species (ROS); DNA damage and DNA repair; cell cycle; and apoptosis. The majority of the 71 DEGs were upregulated and the most upregulated DEGs included a number of immunoglobulin kappa variable genes, and other immune-related genes, e.g., CD86 molecule (CD86), interleukin 2 receptor gamma (IL2RG), and interferon, alpha-inducible protein 6 (IFI6). Upregulated genes preferentially associated with other gene ontologies (GO) were, e.g., STAT1, MMP9, TOP2A, and BRCA2. Biofunctional analysis revealed pathways related to immunogenic functions. Further data analysis focused on the set of non-intersecting 358 DEGs derived from the comparison group of HT vs. TN, and on the set of 950 DEGs from the intersection of all four comparison groups. In conclusion, this study indicates that, besides immune/ inflammation-related genes, also genes associated with oxidative stress, ROS, DNA

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“…TSAbs also upregulate various growth factors and enhance tumor invasiveness [5,6]. Autoimmunity of GD and altered host immune tolerance further increases the risk of thyroid cancer [7,8].…”

Section: Introductionmentioning

confidence: 99%

Prognosis of papillary thyroid cancer in patients with Graves’ disease: a propensity score-matched analysis

Kwon

Moon

2020

World J Surg Onc

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Background Patients with Graves’ disease (GD) are at a 2.5 times higher risk of developing thyroid cancer than the general population. Previous studies reported conflicting results about the prognosis of thyroid cancer concomitant with GD. This study aimed to investigate the effect of GD to the recurrence rates of papillary thyroid carcinoma (PTC). Methods We reviewed 3628 patients who underwent total thyroidectomy for PTC at the Ewha Womans University Medical Center from January 2006 to June 2014. Of those, 114 patients had non-occult PTC with concomitant GD. To reduce potential confounding effects and selection bias, we conducted 1:5 propensity score matching and analyzed the recurrence-free survival. Results Thyroid cancer in patients with GD showed lower rate of lymphatic invasion (1.8% vs. 6.7%; p = 0.037), microscopic resection margin involvement (0.9% vs. 5.8%; p = 0.024), and lymph node metastasis (29.8% vs. 37.3%; p = 0.001) than in patients without GD, respectively. During the median follow-up of 94.1 months, recurrence occurred in one patient (0.9%) with GD. After propensity score matching for adjusting clinicopathological features, 5-year recurrence-free survival was comparable between patients with GD and euthyroid patients (100% vs. 98.4%, p = 0.572). Both tumor size [hazard ratio (HR) 1.585, p < 0.001] and lymph node metastasis (HR for N1a 3.067, p = 0.024; HR for N1b 15.65, p < 0.001) were predictive factors for recurrence-free survival, while GD was not associated with the recurrence. Conclusions Our data suggest that GD does not affect the prognosis of PTC. Thyroid cancer in patients with GD is not more aggressive than in euthyroid patients.

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Thyroid autoimmune disorders and cancer

Cited by 112 publications

References 182 publications

Immune cell confrontation in the papillary thyroid carcinoma microenvironment

Immune cell confrontation in the papillary thyroid carcinoma microenvironment

Genetic relationship between Hashimoto`s thyroiditis and papillary thyroid carcinoma with coexisting Hashimoto`s thyroiditis

Prognosis of papillary thyroid cancer in patients with Graves’ disease: a propensity score-matched analysis

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