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Thyroid Cancer Screening Using Tumor-Associated DN T Cells as Immunogenomic Markers

BACKGROUND: Thyroid nodules are an extremely common entity, and surgery is considered the ultimate diagnostic strategy in those with unclear malignant potential. Unfortunately, strategies aiming to predict the risk of malignancy have inadequate specificity. Our group recently found that the microenv...

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Autores principales: Imam, Shahnawaz, Paparodis, Rodis D., Rafiqi, Shafiya Imtiaz, Ali, Sophia, Niaz, Azra, Kanzy, Abed, Tovar, Yara E., Madkhali, Mohammed A., Elsherif, Ahmed, Khogeer, Feras, Zahid, Zeeshan A., Sarwar, Haider, Karim, Tamanna, Salim, Nancy, Jaume, Juan C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9186057/
https://www.ncbi.nlm.nih.gov/pubmed/35692772
http://dx.doi.org/10.3389/fonc.2022.891002
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author Imam, Shahnawaz
Paparodis, Rodis D.
Rafiqi, Shafiya Imtiaz
Ali, Sophia
Niaz, Azra
Kanzy, Abed
Tovar, Yara E.
Madkhali, Mohammed A.
Elsherif, Ahmed
Khogeer, Feras
Zahid, Zeeshan A.
Sarwar, Haider
Karim, Tamanna
Salim, Nancy
Jaume, Juan C.
author_facet Imam, Shahnawaz
Paparodis, Rodis D.
Rafiqi, Shafiya Imtiaz
Ali, Sophia
Niaz, Azra
Kanzy, Abed
Tovar, Yara E.
Madkhali, Mohammed A.
Elsherif, Ahmed
Khogeer, Feras
Zahid, Zeeshan A.
Sarwar, Haider
Karim, Tamanna
Salim, Nancy
Jaume, Juan C.
author_sort Imam, Shahnawaz
collection PubMed
description BACKGROUND: Thyroid nodules are an extremely common entity, and surgery is considered the ultimate diagnostic strategy in those with unclear malignant potential. Unfortunately, strategies aiming to predict the risk of malignancy have inadequate specificity. Our group recently found that the microenvironment of thyroid cancer is characterized by an enhanced immune invasion and activated immune response mediated by double-negative T lymphocytes (DN T) (CD3(+)CD4(-)CD8(-)), which are believed to enable or promote tumorigenesis. In the present work, we try to use the DN T cells’ proportion in thyroid fine-needle aspiration (FNA) material as a predictor of the risk of malignancy. METHODS: We recruited 127 patients and obtained ultrasound-guided FNA samples from subjects with cytology-positive or suspicious for malignancy and from those with benign nodular goiter associated with compressive symptoms (such as dysphagia, shortness of breath, or hoarseness), Hashimoto thyroiditis, and Graves’ disease. Out of 127, we investigated 46 FNA samples of patients who underwent total thyroidectomy and for which postoperative histological diagnosis by the academic pathologists was available. We specifically measured the number of cells expressing CD3(+)CD4(-)CD8(-) (DN T) as a function of total CD3(+) cells in FNA samples using flow cytometry. We correlated their FNA DN T-cell proportions with the pathological findings. RESULTS: The DN T cells were significantly more abundant in lymphocytic infiltrates of thyroid cancer cases compared to benign nodule controls (p < 0.0001). When the DN T-cell population exceeded a threshold of 9.14%, of total CD3(+) cells, the negative likelihood ratio of being cancer-free was 0.034 (96.6% sensitivity, 95% CI, 0.915–1.000, p < 0.0001). DN T cells at <9.14% were not found in any subject with benign disease (specificity 100%). The high specificity of the test is promising, since it abolishes a false-positive diagnosis and in turn unnecessary surgical procedures. CONCLUSION: The present study proposes DN T cells’ proportion as a preoperative diagnostic signature for thyroid cancer that with integration of RNA transcriptomics can provide a simplified technology based on the PCR assay for the ease of operation.
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spelling pubmed-91860572022-06-11 Thyroid Cancer Screening Using Tumor-Associated DN T Cells as Immunogenomic Markers Imam, Shahnawaz Paparodis, Rodis D. Rafiqi, Shafiya Imtiaz Ali, Sophia Niaz, Azra Kanzy, Abed Tovar, Yara E. Madkhali, Mohammed A. Elsherif, Ahmed Khogeer, Feras Zahid, Zeeshan A. Sarwar, Haider Karim, Tamanna Salim, Nancy Jaume, Juan C. Front Oncol Oncology BACKGROUND: Thyroid nodules are an extremely common entity, and surgery is considered the ultimate diagnostic strategy in those with unclear malignant potential. Unfortunately, strategies aiming to predict the risk of malignancy have inadequate specificity. Our group recently found that the microenvironment of thyroid cancer is characterized by an enhanced immune invasion and activated immune response mediated by double-negative T lymphocytes (DN T) (CD3(+)CD4(-)CD8(-)), which are believed to enable or promote tumorigenesis. In the present work, we try to use the DN T cells’ proportion in thyroid fine-needle aspiration (FNA) material as a predictor of the risk of malignancy. METHODS: We recruited 127 patients and obtained ultrasound-guided FNA samples from subjects with cytology-positive or suspicious for malignancy and from those with benign nodular goiter associated with compressive symptoms (such as dysphagia, shortness of breath, or hoarseness), Hashimoto thyroiditis, and Graves’ disease. Out of 127, we investigated 46 FNA samples of patients who underwent total thyroidectomy and for which postoperative histological diagnosis by the academic pathologists was available. We specifically measured the number of cells expressing CD3(+)CD4(-)CD8(-) (DN T) as a function of total CD3(+) cells in FNA samples using flow cytometry. We correlated their FNA DN T-cell proportions with the pathological findings. RESULTS: The DN T cells were significantly more abundant in lymphocytic infiltrates of thyroid cancer cases compared to benign nodule controls (p < 0.0001). When the DN T-cell population exceeded a threshold of 9.14%, of total CD3(+) cells, the negative likelihood ratio of being cancer-free was 0.034 (96.6% sensitivity, 95% CI, 0.915–1.000, p < 0.0001). DN T cells at <9.14% were not found in any subject with benign disease (specificity 100%). The high specificity of the test is promising, since it abolishes a false-positive diagnosis and in turn unnecessary surgical procedures. CONCLUSION: The present study proposes DN T cells’ proportion as a preoperative diagnostic signature for thyroid cancer that with integration of RNA transcriptomics can provide a simplified technology based on the PCR assay for the ease of operation. Frontiers Media S.A. 2022-05-27 /pmc/articles/PMC9186057/ /pubmed/35692772 http://dx.doi.org/10.3389/fonc.2022.891002 Text en Copyright © 2022 Imam, Paparodis, Rafiqi, Ali, Niaz, Kanzy, Tovar, Madkhali, Elsherif, Khogeer, Zahid, Sarwar, Karim, Salim and Jaume https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Imam, Shahnawaz
Paparodis, Rodis D.
Rafiqi, Shafiya Imtiaz
Ali, Sophia
Niaz, Azra
Kanzy, Abed
Tovar, Yara E.
Madkhali, Mohammed A.
Elsherif, Ahmed
Khogeer, Feras
Zahid, Zeeshan A.
Sarwar, Haider
Karim, Tamanna
Salim, Nancy
Jaume, Juan C.
Thyroid Cancer Screening Using Tumor-Associated DN T Cells as Immunogenomic Markers
title Thyroid Cancer Screening Using Tumor-Associated DN T Cells as Immunogenomic Markers
title_full Thyroid Cancer Screening Using Tumor-Associated DN T Cells as Immunogenomic Markers
title_fullStr Thyroid Cancer Screening Using Tumor-Associated DN T Cells as Immunogenomic Markers
title_full_unstemmed Thyroid Cancer Screening Using Tumor-Associated DN T Cells as Immunogenomic Markers
title_short Thyroid Cancer Screening Using Tumor-Associated DN T Cells as Immunogenomic Markers
title_sort thyroid cancer screening using tumor-associated dn t cells as immunogenomic markers
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9186057/
https://www.ncbi.nlm.nih.gov/pubmed/35692772
http://dx.doi.org/10.3389/fonc.2022.891002
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