CD66b<sup>+</sup> Tumor-Infiltrating Neutrophil-like Monocytes as Potential Biomarkers for Clinical Decision-Making in Thyroid Cancer

<i>Background and Objectives</i>: Thyroid nodules are a common endocrine disorder, with 10–15% exhibiting malignancy. Accurate differentiation of malignant and benign nodules is crucial for optimizing treatment outcomes. Current diagnostic tools, such as the Bethesda classification and f...

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Main Authors: Hamdullah Yanik, Ilgin Demir, Ertugrul Celik, Ece Tavukcuoglu, Ibrahim Burak Bahcecioglu, Adile Begum Bahcecioglu, Mehmet Mert Hidiroglu, Sumeyra Guler, Nese Ersoz Gulcelik, Mehmet Ali Gulcelik, Kerim Bora Yilmaz, Gunes Esendagli
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Language:English
Published: MDPI AG 2025-07-01
Series:Medicina
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Online Access:https://www.mdpi.com/1648-9144/61/7/1256
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author Hamdullah Yanik
Ilgin Demir
Ertugrul Celik
Ece Tavukcuoglu
Ibrahim Burak Bahcecioglu
Adile Begum Bahcecioglu
Mehmet Mert Hidiroglu
Sumeyra Guler
Nese Ersoz Gulcelik
Mehmet Ali Gulcelik
Kerim Bora Yilmaz
Gunes Esendagli
author_facet Hamdullah Yanik
Ilgin Demir
Ertugrul Celik
Ece Tavukcuoglu
Ibrahim Burak Bahcecioglu
Adile Begum Bahcecioglu
Mehmet Mert Hidiroglu
Sumeyra Guler
Nese Ersoz Gulcelik
Mehmet Ali Gulcelik
Kerim Bora Yilmaz
Gunes Esendagli
author_sort Hamdullah Yanik
collection DOAJ
description <i>Background and Objectives</i>: Thyroid nodules are a common endocrine disorder, with 10–15% exhibiting malignancy. Accurate differentiation of malignant and benign nodules is crucial for optimizing treatment outcomes. Current diagnostic tools, such as the Bethesda classification and fine-needle aspiration biopsy (FNAB), are limited in sensitivity and specificity, particularly in indeterminate cases. Tumor-infiltrating immune cells (TIICs) in the tumor microenvironment (TME) play a significant role in thyroid cancer progression. CD66b<sup>+</sup> neutrophil-like monocytes constitute a novel subset of myeloid cells that are implicated in the modulation of anti-tumor immune responses, but their role in thyroid cancer remains unclear. <i>Materials and Methods:</i> Peripheral blood and thyroid nodule tissue samples were obtained from 24 patients with papillary thyroid carcinoma, and from 10 patients who underwent surgery for symptoms of tracheal compression due to benign thyroid nodules. Myeloid cell populations were assayed by flow cytometric immunophenotyping with CD45, HLA-DR, CD14, and CD66b. The data were statistically analyzed with the clinical properties of the patients. <i>Results:</i> The neutrophil-like monocytes, which were determined as HLA-DR<sup>+</sup>CD14<sup>+</sup>CD66b<sup>+</sup> cells, found in the circulation (11.9 ± 2.4% of total mononuclear immune cells) of the patients with papillary thyroid carcinoma, were significantly elevated (<i>p</i> < 0.001). Accordingly, these cells were more frequently detected in tumor tissues (21.1 ± 2.1% of total tumor-infiltrating immune cells) compared to non-tumor thyroid tissues (<i>p</i> = 0.0231). The infiltration levels of neutrophil-like monocytes were significantly higher in malignant nodules as well as in the peripheral blood of the papillary thyroid carcinoma patients compared to the samples obtained from the patients with benign nodules. The tumor tissues exhibited increased immune cell infiltration and harbored CD66b-expressing neutrophil-like HLA-DR<sup>+</sup>CD14<sup>+</sup> monocytic cells, which indicates an inflammatory milieu in malignant thyroid cancer. <i>Conclusions:</i> This study identifies neutrophil-like monocytes as a potential biomarker for differentiating malignant and benign thyroid nodules. Elevated levels of this novel subtype of immune cells in malignant tissues suggest their role in tumor progression and their utility in enhancing diagnostic accuracy. Incorporating these findings into clinical practice may refine surgical decision-making and improve outcomes through personalized diagnostic and therapeutic strategies, particularly for radioiodine-refractory thyroid cancer.
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spelling doaj-art-d12bbc4340284a5e978cefd2581ea8202025-08-20T03:58:31ZengMDPI AGMedicina1010-660X1648-91442025-07-01617125610.3390/medicina61071256CD66b<sup>+</sup> Tumor-Infiltrating Neutrophil-like Monocytes as Potential Biomarkers for Clinical Decision-Making in Thyroid CancerHamdullah Yanik0Ilgin Demir1Ertugrul Celik2Ece Tavukcuoglu3Ibrahim Burak Bahcecioglu4Adile Begum Bahcecioglu5Mehmet Mert Hidiroglu6Sumeyra Guler7Nese Ersoz Gulcelik8Mehmet Ali Gulcelik9Kerim Bora Yilmaz10Gunes Esendagli11Department of Basic Oncology, Cancer Institute, Hacettepe University, Ankara 06230, TurkeyDepartment of General Surgery, University of Health Sciences Gulhane Training and Research Hospital, Ankara 06010, TurkeyDepartment of Pathology, University of Health Sciences Gulhane Training and Research Hospital, Ankara 06010, TurkeyDepartment of Basic Oncology, Cancer Institute, Hacettepe University, Ankara 06230, TurkeyDepartment of Surgical Oncology, University of Health Sciences Gulhane Training and Research Hospital, Ankara 06010, TurkeyDepartment of Endocrinology and Metabolism, Gulhane Research and Training Hospital, University of Health Sciences, Ankara 06010, TurkeyDepartment of General Surgery, University of Health Sciences Gulhane Training and Research Hospital, Ankara 06010, TurkeyDepartment of Surgical Oncology, University of Health Sciences Gulhane Training and Research Hospital, Ankara 06010, TurkeyDepartment of Endocrinology and Metabolism, Gulhane Research and Training Hospital, University of Health Sciences, Ankara 06010, TurkeyDepartment of Surgical Oncology, University of Health Sciences Gulhane Training and Research Hospital, Ankara 06010, TurkeyDepartment of General Surgery, University of Health Sciences Gulhane Training and Research Hospital, Ankara 06010, TurkeyDepartment of Basic Oncology, Cancer Institute, Hacettepe University, Ankara 06230, Turkey<i>Background and Objectives</i>: Thyroid nodules are a common endocrine disorder, with 10–15% exhibiting malignancy. Accurate differentiation of malignant and benign nodules is crucial for optimizing treatment outcomes. Current diagnostic tools, such as the Bethesda classification and fine-needle aspiration biopsy (FNAB), are limited in sensitivity and specificity, particularly in indeterminate cases. Tumor-infiltrating immune cells (TIICs) in the tumor microenvironment (TME) play a significant role in thyroid cancer progression. CD66b<sup>+</sup> neutrophil-like monocytes constitute a novel subset of myeloid cells that are implicated in the modulation of anti-tumor immune responses, but their role in thyroid cancer remains unclear. <i>Materials and Methods:</i> Peripheral blood and thyroid nodule tissue samples were obtained from 24 patients with papillary thyroid carcinoma, and from 10 patients who underwent surgery for symptoms of tracheal compression due to benign thyroid nodules. Myeloid cell populations were assayed by flow cytometric immunophenotyping with CD45, HLA-DR, CD14, and CD66b. The data were statistically analyzed with the clinical properties of the patients. <i>Results:</i> The neutrophil-like monocytes, which were determined as HLA-DR<sup>+</sup>CD14<sup>+</sup>CD66b<sup>+</sup> cells, found in the circulation (11.9 ± 2.4% of total mononuclear immune cells) of the patients with papillary thyroid carcinoma, were significantly elevated (<i>p</i> < 0.001). Accordingly, these cells were more frequently detected in tumor tissues (21.1 ± 2.1% of total tumor-infiltrating immune cells) compared to non-tumor thyroid tissues (<i>p</i> = 0.0231). The infiltration levels of neutrophil-like monocytes were significantly higher in malignant nodules as well as in the peripheral blood of the papillary thyroid carcinoma patients compared to the samples obtained from the patients with benign nodules. The tumor tissues exhibited increased immune cell infiltration and harbored CD66b-expressing neutrophil-like HLA-DR<sup>+</sup>CD14<sup>+</sup> monocytic cells, which indicates an inflammatory milieu in malignant thyroid cancer. <i>Conclusions:</i> This study identifies neutrophil-like monocytes as a potential biomarker for differentiating malignant and benign thyroid nodules. Elevated levels of this novel subtype of immune cells in malignant tissues suggest their role in tumor progression and their utility in enhancing diagnostic accuracy. Incorporating these findings into clinical practice may refine surgical decision-making and improve outcomes through personalized diagnostic and therapeutic strategies, particularly for radioiodine-refractory thyroid cancer.https://www.mdpi.com/1648-9144/61/7/1256thyroid cancerCD66+ monocytescancer diagnosismonocyte subtypesneutrophil
spellingShingle Hamdullah Yanik
Ilgin Demir
Ertugrul Celik
Ece Tavukcuoglu
Ibrahim Burak Bahcecioglu
Adile Begum Bahcecioglu
Mehmet Mert Hidiroglu
Sumeyra Guler
Nese Ersoz Gulcelik
Mehmet Ali Gulcelik
Kerim Bora Yilmaz
Gunes Esendagli
CD66b<sup>+</sup> Tumor-Infiltrating Neutrophil-like Monocytes as Potential Biomarkers for Clinical Decision-Making in Thyroid Cancer
Medicina
thyroid cancer
CD66+ monocytes
cancer diagnosis
monocyte subtypes
neutrophil
title CD66b<sup>+</sup> Tumor-Infiltrating Neutrophil-like Monocytes as Potential Biomarkers for Clinical Decision-Making in Thyroid Cancer
title_full CD66b<sup>+</sup> Tumor-Infiltrating Neutrophil-like Monocytes as Potential Biomarkers for Clinical Decision-Making in Thyroid Cancer
title_fullStr CD66b<sup>+</sup> Tumor-Infiltrating Neutrophil-like Monocytes as Potential Biomarkers for Clinical Decision-Making in Thyroid Cancer
title_full_unstemmed CD66b<sup>+</sup> Tumor-Infiltrating Neutrophil-like Monocytes as Potential Biomarkers for Clinical Decision-Making in Thyroid Cancer
title_short CD66b<sup>+</sup> Tumor-Infiltrating Neutrophil-like Monocytes as Potential Biomarkers for Clinical Decision-Making in Thyroid Cancer
title_sort cd66b sup sup tumor infiltrating neutrophil like monocytes as potential biomarkers for clinical decision making in thyroid cancer
topic thyroid cancer
CD66+ monocytes
cancer diagnosis
monocyte subtypes
neutrophil
url https://www.mdpi.com/1648-9144/61/7/1256
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