Inflammatory Components of the Thyroid Cancer Microenvironment: An Avenue for Identification of Novel Biomarkers

Jarboe, Tara; Tuli, Neha; Chakraborty, Sanjukta; Maniyar, Rachana; DeSouza, Nicole; Li, Xiumin; Moscatello, Augustine; Geliebter, Jan; Tiwari, Raj K.

doi:10.1007/978-3-030-83282-7_1

Cited by 6 publications

(3 citation statements)

References 151 publications

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“…Tumor- antagonizing immune cells consist of effector T cells, NK cells, dendritic cells (DCs), and M1 polarized macrophages; while tumor-promoting immune cells include lymphoid lineage Treg cells, myeloid origin TAMs (M2 TAMs), tumor-associated neutrophils (TANs), tolerogenic DCs (tDCs), and other kinds of suppressive cells. The major suppressors that help in creating a tumor-promoting microenvironment are all kinds of Treg cells (30).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2022

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BackgroundThyroid 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.MethodsWe 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.ResultsThe 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.ConclusionThe 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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Section: Discussionmentioning

confidence: 99%

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

et al. 2022

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“…We know that chronic inflammation can induce a range of inflammatory diseases, including malignancies ( 79 ). A review of the literature revealed that natural products affect the inflammatory response by regulating exosomal ncRNAs.…”

Section: Natural Drugs Regulate Tumor Genesis and Development By Regu...mentioning

confidence: 99%

Natural products exert anti-tumor effects by regulating exosomal ncRNA

Liu

Guan

et al. 2022

Front. Oncol.

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Currently, more than 60% of the approved anti-cancer drugs come from or are related to natural products. Natural products and exosomal non-coding RNAs (ncRNAs) exert anti-cancer effects through various regulatory mechanisms, which are of great research significance. Exosomes are a form of intercellular communication and contain ncRNAs that can act as intercellular signaling molecules involved in the metabolism of tumor cells. This review exemplifies some examples of natural products whose active ingredients can play a role in cancer prevention and treatment by regulating exosomal ncRNAs, with the aim of illustrating the mechanism of action of exosomal ncRNAs in cancer prevention and treatment. Meanwhile, the application of exosomes as natural drug delivery systems and predictive disease biomarkers in cancer prevention and treatment is introduced, providing research ideas for the development of novel anti-tumor drugs.

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“…previously discovered (1). Changes in the immune microenvironment have a significant impact on the biological behavior of tumor cells (7,8), which is one of the important features of tumor heterogeneity. Immunotherapy, which has been widely recognized as a treatment for solid tumors, is a good alternative treatment for papillary thyroid carcinoma with poor response to routine treatment (7).…”

Section: Introductionmentioning

confidence: 99%

Exploring the correlation analysis of immune microenvironment, mutation burden and prognosis of papillary thyroid carcinoma based on Estimate algorithm

Wang¹,

He²,

Cao³

et al. 2022

Gland Surg

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Background: This study aimed to investigate the correlation between immune infiltration and tumor mutational burden (TMB) in papillary thyroid carcinoma.Methods: Transcriptome sequencing data sets, gene mutation data sets, and clinical data sets were downloaded from The Cancer Genome Atlas (TCGA) database. The immune and papillary carcinoma stromal scores were calculated using the "Estimate" package of R software. The relationship between the immune score, stromal score, TMB, and papillary thyroid carcinoma progression-free survival was analyzed.Pearson's test was used to analyze the correlation between the immune score, stromal score, and TMB. Results:The stromal score and immune score of papillary thyroid carcinoma tissue were lower than those of normal thyroid tissue (P=0.008 and P<0.001, respectively). There was no significant difference in progression-free survival between the high stromal and low stromal score groups (P=0.075). The progression-free survival of the high immune score group was better than that of the low immune score group (P=0.029), and the progression-free survival of the low TMB group was better than that of the high TMB group (P<0.001). The high immune score, low TMB group had the best prognosis (P=0.003).Univariate Cox analysis showed that age, pathological stage, and TMB were risk factors for progression-free survival [hazard ratio (HR) >1, P<0.05], and that the immune score was a protective factor for progressionfree survival (HR <1, P<0.05). Multivariate Cox analysis showed that age and TMB were independent risk factors for progression-free survival (HR >1, P<0.05), and that the immune score was an independent protective factor for progression-free survival (HR <1, P<0.05). Correlation analysis showed that the immune and stromal score were both negatively correlated with TMB (r=−0.26, P=0.031 and r=−0.41, P=0.028, respectively). Conclusions:The immune and stromal scores of papillary thyroid carcinoma were negatively correlated with TMB. Thyroid cancer gene mutations inhibit immune cell infiltration and alter the thyroid cancer microenvironment. The immune score was an independent protective factor for progression-free survival, while TMB was an independent risk factor, both of which can be used for clinical prognosis assessment.Combined immunological and genomic analysis of papillary thyroid carcinoma can reveal potential prognostic markers and therapeutic targets and provide clues for the tumor immune escape mechanism.

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Inflammatory Components of the Thyroid Cancer Microenvironment: An Avenue for Identification of Novel Biomarkers

Cited by 6 publications

References 151 publications

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

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

Natural products exert anti-tumor effects by regulating exosomal ncRNA

Exploring the correlation analysis of immune microenvironment, mutation burden and prognosis of papillary thyroid carcinoma based on Estimate algorithm

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