Infiltration of a mixture of different immune cells may be related to molecular profile of differentiated thyroid cancer

Cunha, Lucas Leite; Morari, Elaine Cristina; Guihen, Ana Carolina Trindade; Razolli, Daniela S.; Gerhard, Renê; Nonogaki, Suely; Soares, Fernando Augusto; Vassallo, José; Ward, Laura Sterian

doi:10.1530/erc-11-0285

Cited by 29 publications

(28 citation statements)

References 15 publications

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“…Recently, Kaiser et al (2012) found that chronically stimulated CD8C lymphocytes become sensitive to B7H1-mediated functional inhibition upon low antigen detection, suggesting that immune escape may be orchestrated by both B7H1 mechanism and tumor antigen density. In fact, Kaiser's results are coherent with our previous data, demonstrating that the pattern of immune cells infiltrating DTC is closely associated with molecular markers of these tumors (Cunha et al 2012a). Lymph node metastatic tissues had lower levels of B7H1 than the primary tumor, suggesting an exhaustion of T-cell activation.…”

Section: Discussionsupporting

confidence: 88%

“…In fact, Waeckerle-Men et al (2007) demonstrated that B7H1 has a negative effect on CD8C lymphocyte activation. Blank et al (2006) demonstrated that the blockade of B7H1 on human tumors resulted in enhanced cytolytic activity of tumor-infiltrating lymphocytes and cytokine production of T-helper cells when interacting directly with the tumor, explaining the aggressiveness associated with B7H1 expression in DTC even that these tumors are frequently associated with signals of antitumor immune response , 2012a, Cunha & Ward 2012. Recently, Kaiser et al (2012) found that chronically stimulated CD8C lymphocytes become sensitive to B7H1-mediated functional inhibition upon low antigen detection, suggesting that immune escape may be orchestrated by both B7H1 mechanism and tumor antigen density.…”

Section: Discussionmentioning

confidence: 99%

“…Tissue sections were then incubated overnight at 6 8C, with rabbit anti-B7H1 polyclonal antibody (prediluted; ab82059; Abcam, Cambridge, UK). We also investigated the presence of different tumor-infiltrating lymphocytes (CD3-, CD4-, CD8-, CD20-, and FoxP3-positive lymphocytes), tumorassociated macrophages (CD68C cells), and myeloidderived suppressor cells (colocalization of CD33 and CD11b), as described previously (Cunha et al 2012a). The advanced biotin-free polymer detection system was used (DAKO, Carpinteria, CA, USA).…”

Section: Immunohistochemistrymentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Immunohistochemistrymentioning

confidence: 99%

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Differentiated thyroid carcinomas may elude the immune system by B7H1 upregulation

Cunha¹,

Marcello²,

Morari³

et al. 2012

Endocrine-Related Cancer

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“…papillary thyroid carcinoma (PTC), FA) and normal tissues by IHC (Cunha et al 2012). Tumor-associated macrophages (TAMs) were found in malignant (82.11%) and less frequently in benign thyroid tumors (33.91%).…”

Section: :10mentioning

confidence: 99%

Perspectives for immunotherapy in endocrine cancer

Latteyer¹,

Tiedje²,

Schilling³

et al. 2016

Endocrine-Related Cancer

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The fight against cancer has seen major breakthroughs in recent years. More than a decade ago, tyrosine kinase inhibitors targeting constitutively activated signaling cascades within the tumor inaugurated a new era of oncological therapy. Recently, immunotherapy with immune checkpoint inhibitors has started to revolutionize the treatment of several malignancies, most notably malignant melanoma, leading to the renaissance and the long-awaited breakthrough of immunooncology. This review provides an overview of the basis of immunotherapy from its initial concepts of antitumor immunity and cell-based therapy to the development of immune checkpoint inhibitors and discusses published studies and the perspectives of immunooncology for the treatment of endocrine malignancies.

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“…An expansion of various regulatory cell populations such as DCs [72,75,76], Tregs [67,74,77,78] or myeloid-derived suppressor cells [67,79,80] plays most probably a crucial role in this process. In thyroid carcinoma the process of infiltration with particular immune cell populations, including tumour associated monocytes, myeloid-derived suppressor cells, FoxP3 + Tregs, and other lymphocytic subsets, was correlated with tumour type and level of aggressiveness [67,[81][82][83]. Also, the role of DCs mediated immunoregulatory processes was postulated in the development of thyroid malignancies.…”

Section: Thyroid Cancermentioning

confidence: 99%

Dendritic cells in autoimmune disorders and cancer of the thyroid

Lewiński

Śliwka

Stasiołek

2014

Folia Histochem Cytobiol.

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Dendritic cells (DCs), considered as one of the crucial immune regulatory populations, are implicated in the immune pathology of various disorders. Also in the thyroid gland, DCs were shown to be involved in early and chronic phases of various types of autoimmunity -including Hashimoto's thyroiditis and Graves' disease. In thyroid malignant processes, DCs are suggested as an important element of both tumour defence and tumour immune evasion mechanisms. Recent findings emphasize a crucial role of interactions between particular DC subsets and other regulatory cell populations (e.g. FoxP3+ regulatory T cells) in thyroid pathology. Additionally, an increasing attention has been paid to the control of DC function by thyrometabolic conditions.

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Infiltration of a mixture of different immune cells may be related to molecular profile of differentiated thyroid cancer

Cited by 29 publications

References 15 publications

Differentiated thyroid carcinomas may elude the immune system by B7H1 upregulation

Differentiated thyroid carcinomas may elude the immune system by B7H1 upregulation

Perspectives for immunotherapy in endocrine cancer

Dendritic cells in autoimmune disorders and cancer of the thyroid

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