Bruna C Bertol1, Jéssica N G de Araújo2, Ibrahim A Sadissou3, Paulin Sonon1, Fabrício C Dias3, Raul H Bortolin2, Nathalie L de Figueiredo-Feitosa4, Luiz C Conti de Freitas5, Sheila R de Miranda Henrique Tarrapp6, Carlos C de Oliveira Ramos7, André D Luchessi2,8, Janaina C O C de Freitas2,8, Léa M Z Maciel4, Vivian N Silbiger2,8, Eduardo A Donadi1,3. 1. Postgraduate Program of Basic and Applied Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil. 2. Postgraduate Program of Pharmaceutical Sciences, Federal University of Rio Grande do Norte, Natal, Brazil. 3. Department of Medicine, Division of Clinical Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil. 4. Department of Medicine, Division of Endocrinology and Metabolism, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil. 5. Department of Medicine, Division of Head And Neck Surgery, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil. 6. Division of Head And Neck Surgery, Hospital Liga Norte Riograndense Contra o Câncer, Natal, Brazil. 7. Division of Pathology, Hospital Liga Norte Riograndense Contra o Câncer, Natal, Brazil. 8. Department of Clinical Analysis and Toxicology, Federal University of Rio Grande do Norte, Natal, Brazil.
Abstract
BACKGROUND: Increasing evidence shows that chronic inflammation plays an important role in thyroid tumorigenesis. Cytokines as central mediators in inflammatory microenvironment can present both pro-tumour and anti-tumour effects and cytokine release may be influenced by soluble HLA-G (sHLA-G), an immune checkpoint molecule whose expression can also be induced by certain cytokines. AIM: To understand the role of these soluble factors in papillary thyroid cancer (PTC). METHODS: We evaluated plasma levels of sHLA-G and of 13 cytokines using ELISA and flow cytometry, respectively, in PTC patients at two time points: pre- and post-thyroidectomy; and control subjects. RESULTS: Compared with controls, IL-6 levels were increased, while IL-1β, IFN-α and TGF-β1 levels were decreased in pre-thyroidectomy PTC patients. IFN-α and TGF-β1 efficiently discriminated patients from controls and were associated with extrathyroidal extension and lymph node metastasis, respectively. In addition, TNF and IL-13 were associated with male gender, lymph node metastasis and Hashimoto thyroiditis, and sHLA-G with tumour invasion. Compared with pre-thyroidectomy, IL-4, IL-10, TNF, IFN-α and TGF-β1 levels were increased in post-thyroidectomy. CONCLUSION: There are significant changes in the cytokine profile after surgical removal of the thyroid tumour, and IFN-α e TGF-β1 showed to be promising cytokines for discriminating PTC patients from controls. We also found that different cytokines are associated with clinicohistopathological characteristics of PTC related to poor prognosis, suggesting that cytokines seem to play an important role in PTC development and management.
BACKGROUND: Increasing evidence shows that chronic inflammation plays an important role in thyroid tumorigenesis. Cytokines as central mediators in inflammatory microenvironment can present both pro-tumour and anti-tumour effects and cytokine release may be influenced by soluble HLA-G (sHLA-G), an immune checkpoint molecule whose expression can also be induced by certain cytokines. AIM: To understand the role of these soluble factors in papillary thyroid cancer (PTC). METHODS: We evaluated plasma levels of sHLA-G and of 13 cytokines using ELISA and flow cytometry, respectively, in PTC patients at two time points: pre- and post-thyroidectomy; and control subjects. RESULTS: Compared with controls, IL-6 levels were increased, while IL-1β, IFN-α and TGF-β1 levels were decreased in pre-thyroidectomy PTC patients. IFN-α and TGF-β1 efficiently discriminated patients from controls and were associated with extrathyroidal extension and lymph node metastasis, respectively. In addition, TNF and IL-13 were associated with male gender, lymph node metastasis and Hashimoto thyroiditis, and sHLA-G with tumour invasion. Compared with pre-thyroidectomy, IL-4, IL-10, TNF, IFN-α and TGF-β1 levels were increased in post-thyroidectomy. CONCLUSION: There are significant changes in the cytokine profile after surgical removal of the thyroid tumour, and IFN-α e TGF-β1 showed to be promising cytokines for discriminating PTC patients from controls. We also found that different cytokines are associated with clinicohistopathological characteristics of PTC related to poor prognosis, suggesting that cytokines seem to play an important role in PTC development and management.