Tumor-Associated Lymphocytes and Increased FoxP3+ Regulatory T Cell Frequency Correlate with More Aggressive Papillary Thyroid Cancer

French, Jena D.; Weber, Zachary; Fretwell, Deborah; Said, Sherif; Klopper, Joshua; Haugen, Bryan R.

doi:10.1210/jc.2009-2564

Cited by 151 publications

(158 citation statements)

References 39 publications

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“…108 In a small PTC patient dataset, Foxp3 C Tregs and VEGF, evaluated by immunohistochemistry, were found in PTC samples and Treg infiltration correlated with disease stage and lymph node metastasis. 109 A higher Treg density was also observed in PTC samples compared with nodular goiter, and positively correlated to the stage of the disease. 93 Accordingly, in a study performed on 124 tissue samples from PTC microcarcinomas, high infiltration of Foxp3 C Treg cells was associated with aggressive features of PTC microcarcinoma.…”

Section: Natural Killer T Cells (Nkt) Gd T Cells and Innate Lymphoidmentioning

confidence: 82%

The immune network in thyroid cancer

2016

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The immune system plays critical roles in tumor prevention, but also in its initiation and progression. Tumors are subjected to immunosurveillance, but cancer cells generate an immunosuppressive microenvironment that favors their escape from immune-mediated elimination. During chronic inflammation, immune cells can contribute to the formation and progression of tumors by producing mitogenic, prosurvival, proangiogenic and lymphangiogenic factors. Thyroid cancer is the most frequent type of endocrine neoplasia and is the most rapidly increasing cancer in the US. In this review, we discuss recent findings on how different immune cells and mediators can contribute to thyroid cancer development and progression.

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Section: Natural Killer T Cells (Nkt) Gd T Cells and Innate Lymphoidmentioning

confidence: 82%

The immune network in thyroid cancer

2016

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“…We previously observed a less aggressive phenotype associated with evidences of immune response against thyroid tumors , Cunha & Ward 2012. Conversely, recent studies observed that infiltration of different subsets of lymphocytes may contribute to tumor progression (French et al 2010, Gogali et al 2012, suggesting the occurrence of an immune escape mechanism. Cancers are known to elude the immune system by different mechanisms.…”

Section: Introductionmentioning

confidence: 84%

Differentiated thyroid carcinomas may elude the immune system by B7H1 upregulation

Cunha¹,

Marcello²,

Morari³

et al. 2012

Endocrine-Related Cancer

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B7H1 is consistently associated with inhibition of the immune system in many solid tumors. However, there is no report about its impact on differentiated thyroid carcinoma (DTC) presentation, aggressiveness, or evolution. Aiming to investigate the role of B7H1 in DTC and correlate this protein with other tumor-infiltrating immune cells, we studied 407 thyroid nodule tissue samples including 293 from DTC patients, all managed according to a same standard protocol. In addition, we obtained 5 normal and 114 benign thyroid lesions. Eighteen out of the 253 papillary thyroid carcinomas were paired with respective metastatic lymph node tissues. B7H1 (CD274) protein expression was assessed by immunohistochemistry and the gene expression was quantified by real-time PCR. Malignant tissues displayed a more intense B7H1 staining and higher mRNA levels than benign tissues (both P!0.0001). We observed a positive linear correlation between higher age at diagnosis and B7H1 mRNA levels (PZ0.02896). Elevated levels of B7H1 protein were associated with the presence of CD4C, CD8C, CD20C, and FoxP3C lymphocytes (all P!0.05); tumor-associated macrophages (P!0.0001); and the presence of myeloid-derived suppressor cells (PZ0.03256). Stage II-IV patients presented higher B7H1 mRNA levels than stage I cases (PZ0.03522). On the contrary, a decreased expression of B7H1 protein was observed in lymph node metastasis (PZ0.0152). In conclusion, our data demonstrate that B7H1 expression is associated with features of aggressiveness, suggesting that this is an immune evasion mechanism of DTC cells.

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“…Gender The incidence of HT in PTCs according to gender was compared in 23 studies (3,4,5,6,7,14,15,19,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38). HT in PTCs was observed in 1677 of 7346 (23%) female patients and in 180 of 573 (11%) male patients.…”

Section: Clinicopathologic Characteristics Of Ptcs With Htmentioning

confidence: 99%

“…In addition, the clinicopathologic characteristics of PTCs with concomitant HT have not been definitely proposed (3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40). Therefore, the present meta-analysis was conducted to clarify the relationship between PTCs and histologically proven conventional HT and to investigate the clinicopathologic features of PTCs with coexistent HT.…”

Section: Introductionmentioning

confidence: 97%

The association between papillary thyroid carcinoma and histologically proven Hashimoto's thyroiditis: a meta-analysis

Lee

Kim

Choi

et al. 2013

European Journal of Endocrinology

282

259

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Objective: No consensus exists on the association between papillary thyroid carcinoma (PTC) and Hashimoto's thyroiditis (HT). To resolve this controversy, this study aimed to evaluate the relationship between the two conditions using a meta-analysis. Methods: We searched relevant published studies using citation databases including PubMed, Embase, and ISI Web of Science. The effect sizes of clinicopathologic parameters were calculated by odds ratio (OR), weighted mean difference, or hazard ratio (HR). The effect sizes were combined using a randomeffects model. Results: Thirty-eight eligible studies including 10 648 PTC cases were selected. Histologically proven HT was identified in 2471 (23.2%) PTCs. HT was more frequently observed in PTCs than in benign thyroid diseases and other carcinomas (ORZ2.8 and 2.4; P!0.001). PTCs with coexisting HT were significantly related to female patients (ORZ2.7; P!0.001), multifocal involvement (ORZ1.5; PZ0.010), no extrathyroidal extension (ORZ1.3; PZ0.002), and no lymph node metastasis (ORZ1.3; PZ0.041). Moreover, PTCs with HT were significantly associated with long recurrence-free survival (HRZ0.6; PZ0.001). Conclusions: Our meta-analysis showed that PTC is significantly associated with pathologically confirmed HT. PTC patients with HT have favorable clinicopathologic characteristics compared with PTCs without HT. However, patients with HT need to be carefully monitored for the development of PTC.

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Tumor-Associated Lymphocytes and Increased FoxP3+ Regulatory T Cell Frequency Correlate with More Aggressive Papillary Thyroid Cancer

Abstract: TAL and high Treg frequency in primary thyroid tumors correlates with more aggressive disease. Future prospective studies may identify Treg frequency as a predictive factor in PTC, and the suppressive effects of Treg should be considered in the design of immune-based therapies.

Cited by 151 publications

References 39 publications

The immune network in thyroid cancer

The immune network in thyroid cancer

Differentiated thyroid carcinomas may elude the immune system by B7H1 upregulation

The association between papillary thyroid carcinoma and histologically proven Hashimoto's thyroiditis: a meta-analysis

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