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Advances in Understanding the Immune Network of Thyroid Cancers

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A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Immunology and Immunotherapy".

Deadline for manuscript submissions: closed (31 March 2023) | Viewed by 12007

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Special Issue Editor

Dr. Stephanie Markovina

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Guest Editor

Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO 63108, USA
Interests: biomarkers; radioresistance; thyroid cancer; cervical cancer

Special Issue Information

Dear Colleagues,

The importance of the immune system in the development of tumors and response to therapy has long been recognized. Mechanisms underlying these influences are now being elucidated for various human malignancies, including primary thyroid cancers. Seminal works delineating the immune landscapes of differentiated, anaplastic, and poorly differentiated thyroid carcinomas, as well as clinical data suggesting promising results with immune checkpoint therapy in some patients with thyroid cancer emphasize the importance of understanding immune contributions to thyroid cancer development and therapeutic response.

We are pleased to invite authors to submit articles addressing the interaction of immune cells, cytokines, and lymph system to thyroid cancer establishment, aggressiveness, and response to therapies including radiation, immune checkpoint therapies, and other immunotherapies, as well as targeted therapies such as BRAF kinase inhibitors and MEK/MAPK pathway inhibitors. Original articles and review articles are welcome.

We look forward to receiving your contributions.

Dr. Stephanie Markovina
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

thyroid cancer
anti-tumor immunity
immune checkpoint inhibitors

Published Papers (6 papers)

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Research

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15 pages, 1332 KiB

Open AccessArticle

Impact of BRAFV600E Mutation on Event-Free Survival in Patients with Papillary Thyroid Carcinoma: A Retrospective Study in a Romanian Population

by Adela Nechifor-Boilă, Ancuţa Zahan, Claudia Bănescu, Valeriu Moldovan, Doina Piciu, Septimiu Voidăzan and Angela Borda

Cancers 2023, 15(16), 4053; https://doi.org/10.3390/cancers15164053 - 11 Aug 2023

Viewed by 951

Abstract

We aimed to evaluate the prognostic value of BRAFV600E mutation in a series of 127 papillary thyroid carcinoma (PTC) cases as a single factor, and in synergic interaction with other standard risk factors. BRAFV600E mutation was assessed by real-time PCR. Event-free survival (EFS) was calculated between the date of the first evaluation and the date of occurrence of an adverse event or the date of the last known status. The prevalence of BRAFV600E mutation was 57.2%. The Kaplan–Meier analysis showed a significant reduction of EFS among cases harboring BRAFV600E mutation compared to non-mutated cases (p = 0.010). In addition, BRAFV600E mutation was found to better predict adverse outcomes when associated with the following risk factors: age ≥ 55 years old (p < 0.001), male gender (p < 0.001), conventional (p = 0.005) and tall cell (p = 0.014) histology, tumor size > 40 mm (p = 0.001), extrathyroidal extension (p = 0.001), multifocality (p = 0.001) and lymph node metastasis (p < 0.001). In univariate analysis, a 3.74-fold increased risk for a reduced EFS (p = 0.018) was found for BRAFV600E-mutated cases, but no increased risk was further confirmed by multivariate analysis. Our results highlight that BRAFV600E mutation cannot be used alone as an independent predictive factor in PTC patients, but is prognostically valuable if integrated in the context of other clinicopathological risk factors. Full article

(This article belongs to the Special Issue Advances in Understanding the Immune Network of Thyroid Cancers)

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20 pages, 1150 KiB

Open AccessArticle

Incidental Node Metastasis as an Independent Factor of Worse Disease-Free Survival in Patients with Papillary Thyroid Carcinoma

by Renan Aguera Pinheiro, Ana Kober Leite, Beatriz Godoi Cavalheiro, Evandro Sobroza de Mello, Luiz Paulo Kowalski and Leandro Luongo Matos

Cancers 2023, 15(3), 943; https://doi.org/10.3390/cancers15030943 - 2 Feb 2023

Cited by 4 | Viewed by 1661

Abstract

Introduction: Papillary thyroid carcinoma (PTC) have high node metastasis rates. Occasionally after thyroidectomy, the pathological report reveals node metastasis unintentionally resected. The present study aimed to evaluate the prognosis of these patients. Methods: A retrospective cohort of patients submitted to thyroidectomy with or without central compartment neck dissection (CCND) due to PTC with a minimum follow-up of five years. Results: A total of 698 patients were included: 320 Nx, 264 pN0-incidental, 37 pN1a-incidental, 32 pN0-CCND and 45 pN1a-CCND. Patients with node metastasis were younger, had larger tumors, higher rates of microscopic extra-thyroidal extension, and angiolymphatic invasion and most received radioiodine therapy. Treatment failure was higher in patients pN1a-incidental and pN1a-CCND (32% and 16%, respectively; p < 0.001—Chi-square test). Disease-free survival (DFS) was lower in patients pN1a-incidental compared to patients Nx and pN0-incidental (p < 0.001 vs. Nx and pN0-incidental and p = 0.005 vs. pN0-CCND) but similar when compared to patients pN1a-CCND (p = 0.091)—Log-Rank test. Multivariate analysis demonstrated as independent risk factors: pT4a (HR = 5.524; 95%CI: 1.380–22.113; p = 0.016), pN1a-incidental (HR = 3.691; 95%CI: 1.556–8.755; p = 0.003), microscopic extra-thyroidal extension (HR = 2.560; 95%CI: 1.303–5.030; p = 0.006) and angiolymphatic invasion (HR = 2.240; 95%CI: 1.077–4.510; p = 0.030). Conclusion: Patients that were pN1a-incidental were independently associated with lower DFS. Full article

(This article belongs to the Special Issue Advances in Understanding the Immune Network of Thyroid Cancers)

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12 pages, 896 KiB

Open AccessArticle

Profile of MicroRNAs Associated with Death Due to Disease Progression in Metastatic Papillary Thyroid Carcinoma Patients

by Ana Kober Leite, Kelly Cristina Saito, Thérèse Rachell Theodoro, Fátima Solange Pasini, Luana Perrone Camilo, Carlos Augusto Rossetti, Beatriz Godoi Cavalheiro, Venâncio Avancini Ferreira Alves, Luiz Paulo Kowalski, Maria Aparecida Silva Pinhal, Edna Teruko Kimura and Leandro Luongo Matos

Cancers 2023, 15(3), 869; https://doi.org/10.3390/cancers15030869 - 31 Jan 2023

Cited by 1 | Viewed by 1647

Abstract

Papillary thyroid carcinoma (PTC) is the most common neoplasm of the endocrine system and has an excellent long-term prognosis, with low rates of distant metastatic disease. Although infrequent, there are cases of deaths directly related to PTC, especially in patients with metastatic disease, and the factors that could be associated with this unfavorable outcome remain a major challenge in clinical practice. Recently, research into genetic factors associated with PTC has gained ground, especially mutations in the TERT promoter and BRAF gene. However, the role of microRNAs remains poorly studied, especially in those patients who have an unfavorable outcome at follow-up. This paper aims to evaluate molecular markers related to the different pathological processes of PTC, as well as the histological characteristics of the neoplasm, and to compare this profile with prognosis and death from the disease using an analysis of patients treated for metastatic disease in a single tertiary cancer center. Evaluation of microRNA expression in paraffin-embedded tumor specimens was carried out by quantitative PCR using the TaqMan^® Low Density Array (TLDA) system. Metastatic patients who died from progression of PTC had higher expressions of miR-101-3p, miR-17-5p, and miR-191-5p when compared to patients with stable metastatic disease. These findings are of great importance but should be considered as preliminary because of the small sample. Full article

(This article belongs to the Special Issue Advances in Understanding the Immune Network of Thyroid Cancers)

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18 pages, 3963 KiB

Open AccessArticle

Recurrence Risk Evaluation in Patients with Papillary Thyroid Carcinoma: Multicenter Machine Learning Evaluation of Lymph Node Variables

by Sung-Woo Jang, Jae-Hyun Park, Hae-Rim Kim, Hyeong-Ju Kwon, Yu-Mi Lee, Suck-Joon Hong and Jong-Ho Yoon

Cancers 2023, 15(2), 550; https://doi.org/10.3390/cancers15020550 - 16 Jan 2023

Cited by 2 | Viewed by 1537

Abstract

Background: Lymph node (LN)-related risk factors have been updated to predict long-term outcomes in patients with papillary thyroid carcinoma (PTC). However, those factors’ analytic appropriateness and general applicability must be validated. This study aimed to assess LN-related risk factors, and suggest new LN-related risk categories. Methods: This multicenter observational cohort study included 1232 patients with PTC with N1 disease treated with a total thyroidectomy and neck dissection followed by radioactive iodine remnant ablation. Results: The median follow-up duration was 117 months. In the follow-up period, structural recurrence occurred in 225 patients (18.3%). Among LN-related variables, the presence of extranodal extension (p < 0.001), the maximal diameter of metastatic LN foci (p = 0.029), the number of retrieved LNs (p = 0.003), the number of metastatic LNs (p = 0.003), and the metastatic LN ratio (p < 0.001) were independent risk factors for structural recurrence. Since these factors showed a nonlinear association with the hazard ratio of recurrence-free survival (RFS) rates, we calculated their optimal cutoff values using the K-means clustering algorithm, selecting 0.2 cm and 1.1 cm for the maximal diameter of metastatic LN foci, 4 and 13 for the number of metastatic LN, and 0.28 and 0.58 for the metastatic LN ratio. The RFS curves of each subgroup classified by these newly determined cutoff values showed significant differences (p < 0.001). Each LN risk group also showed significantly different RFS rates from the others (p < 0.001). Conclusions: In PTC patients with an N1 classification, our novel LN-related risk estimates may help predict long-term outcomes and design postoperative management and follow-up strategies. After further validation studies based on independent datasets, these risk categories might be considered when redefining risk stratification or staging systems. Full article

(This article belongs to the Special Issue Advances in Understanding the Immune Network of Thyroid Cancers)

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Review

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14 pages, 1425 KiB

Open AccessReview

The Tumor Microenvironment and the Estrogen Loop in Thyroid Cancer

by Nerina Denaro, Rebecca Romanò, Salvatore Alfieri, Alessia Dolci, Lisa Licitra, Imperia Nuzzolese, Michele Ghidini, Claudia Bareggi, Valentina Bertaglia, Cinzia Solinas and Ornella Garrone

Cancers 2023, 15(9), 2458; https://doi.org/10.3390/cancers15092458 - 25 Apr 2023

Cited by 2 | Viewed by 2580

Abstract

Thyroid cancer (TC) cells employ multiple signaling pathways, such as PI3K/AKT/mTOR and RAS/Raf/MAPK, fostering cell proliferation, survival and metastasis. Through a complex interplay with immune cells, inflammatory mediators and stroma, TC cells support an immunosuppressive, inflamed, pro-carcinogenic TME. Moreover, the participation of estrogens in TC pathogenesis has previously been hypothesized, in view of the higher TC incidence observed among females. In this respect, the interactions between estrogens and the TME in TC could represent a relevant, unexplored area of research. We thereby collectively reviewed the available evidence concerning the potential carcinogenic role of estrogens in TC, specifically focusing on their crosstalk with the TME. Full article

(This article belongs to the Special Issue Advances in Understanding the Immune Network of Thyroid Cancers)

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19 pages, 1242 KiB

Open AccessReview

The Immune Landscape of Papillary Thyroid Cancer in the Context of Autoimmune Thyroiditis

by Fabiana Pani, Paola Caria, Yoshinori Yasuda, Miyara Makoto, Stefano Mariotti, Laurence Leenhardt, Solmaz Roshanmehr, Patrizio Caturegli and Camille Buffet

Cancers 2022, 14(17), 4287; https://doi.org/10.3390/cancers14174287 - 1 Sep 2022

Cited by 11 | Viewed by 3138

Abstract

Papillary thyroid cancer (PTC) often co-occurs with Hashimoto’s thyroiditis, an association that has long been reported in clinical studies, remaining controversial. Experimental evidence has recently shown that pre-existing thyroiditis has a beneficial effect on PTC growth and progression by a distinctive expansion of effector memory CD8 T cells. Although the link between inflammation and PTC might involve different components of the immune system, a deep characterization of them which includes T cells, B cells and tertiary lymphoid structures, Mye-loid cells, Neutrophils, NK cells and dendritic cells will be desirable. The present review article considers the role of the adaptive and innate immune response surrounding PTC in the context of Hashimoto’s thyroiditis. This review will focus on the current knowledge by in vivo and in vitro studies specifically performed on animals’ models; thyroid cancer cells and human samples including (i) the dual role of tumor-infiltrating lymphocytes; (ii) the emerging role of B cells and tertiary lymphoid structures; (iii) the role of myeloid cells, dendritic cells, and natural killer cells; (iv) the current knowledge of the molecular biomarkers implicated in the complex link between thyroiditis and PTC and the potential implication of cancer immunotherapy in PTC patients in the context of thyroiditis. Full article

(This article belongs to the Special Issue Advances in Understanding the Immune Network of Thyroid Cancers)

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