Interactions between LAMP3+ dendritic cells and T-cell subpopulations promote immune evasion in papillary thyroid carcinoma.

BACKGROUND: The incidence of papillary thyroid cancer (PTC) continues to rise all over the world, 10-15% of the patients have a poor prognosis. Although immunotherapy has been applied in clinical practice, its therapeutic efficacy remains far from satisfactory, necessitating further investigation of the mechanism of PTC immune remodeling and exploration of novel treatment targets. METHODS: This study conducted a single-cell RNA sequencing (scRNA-seq) analysis using 18 surgical tissue specimens procured from 14 patients diagnosed with adjacent tissues, non-progressive PTC or progressive PTC. Key findings were authenticated through spatial transcriptomics RNA sequencing, immunohistochemistry, multiplex immunohistochemistry, and an independent bulk RNA-seq data set containing 502 samples. RESULTS: A total of 151,238 individual cells derived from 18 adjacent tissues, non-progressive PTC and progressive PTC specimens underwent scRNA-seq analysis. We found that progressive PTC exhibits the following characteristics: a significant decrease in overall immune cells, enhanced immune evasion of tumor cells, and disrupted antigen presentation function. Moreover, we identified a subpopulation of lysosomal associated membrane protein 3 (LAMP3+) dendritic cells (DCs) exhibiting heightened infiltration in progressive PTC and associated with advanced T stage and poor prognosis of PTC. LAMP3+ DCs promote CD8+ T cells exhaustion (mediated by NECTIN2-TIGIT) and increase infiltration abundance of regulatory T cells (mediated by chemokine (C-C motif) ligand 17 (CCL17)-chemokine (C-C motif) receptor 4 (CCR4)) establishing an immune-suppressive microenvironment. Ultimately, we unveiled that progressive PTC tumor cells facilitate the retention of LAMP3+ DCs within the tumor microenvironment through NECTIN3-NECTIN2 interactions, thereby rendering tumor cells more susceptible to immune evasion. CONCLUSION: Our findings expound valuable insights into the role of the interaction between LAMP3+ DCs and T-cell subpopulations and offer new and effective ideas and strategies for immunotherapy in patients with progressive PTC.

Diagnostic performance of thyroid imaging reporting and data system (TI-RADS) alone and in combination with contrast-enhanced ultrasonography for the characterization of thyroid nodules.

BACKGROUND: The thyroid imaging reporting and data system (TI-RADS), classified and determined the risk of thyroid nodule malignancy with ultrasound scanning. Contrast-enhanced ultrasound (CEUS) is newly developed methods which could measure perfusion features. OBJECTIVE: The aim of the study was to investigate the value of diagnosing thyroid nodules using TI-RADS combined with CEUS and determine whether improvements were made to the diagnostic accuracy. METHODS: The features of conventional ultrasonography (US) and CEUS ion 117 case of thyroid nodules samples, which were confirmed by fine-needle aspiration and/or surgery, were retrospectively analyzed. The independent US and CEUS predictors for malignancy were determined and quantified using logistic regression analysis. The receiver operating characteristic (ROC) curve analysis was used to compare the diagnostic efficiency of each method in predicting malignant solid thyroid nodules. RESULTS: The TI-RADS + CEUS combination had the highest accuracy (94.02%), sensitivity (94.74%), specificity (93.33%), PPV (93.10%) and NPV (94.92%), significantly greater than that of TI-RADS alone and CEUS alone (χ2 = 8.746, P < 0.001; χ2 = 9.825, P < 0.001). The area under the ROC curve (AUC) of TI-RADS alone, CEUS alone, and combined use of TI-RADS and CEUS were 0.871, 0.884, and 0.942, respectively. The following conventional US and CEUS features based on logistic regression analysis showed significant predictive value for thyroid malignant nodules: Obscure margin, calcification, hypoechoic, low enhancement, rim-like enhancement. CONCLUSIONS: TI-RADS in combination with CEUS has superior diagnostic efficiency in the discrimination of benign and malignant thyroid lesions, compared with TI-RADS and CEUS alone.

Right Atrial Evaluation in Patients With Pulmonary Hypertension: A Real-time 3-Dimensional Transthoracic Echocardiographic Study.

OBJECTIVES: The purpose of this study was to investigate the changes in the morphologic characteristics and performance of the right atrium (RA) that occur secondary to structural remodeling of the right ventricle (RV) in patients with pulmonary hypertension by real-time 3-dimensional echocardiography (3DE). METHODS: Comprehensive 2-dimensional echocardiography and real-time 3DE were performed in 112 patients and 30 healthy control participants. Patients with pulmonary hypertension were divided into 3 subgroups: 1, normal RV dimension (n = 34); 2, RV enlargement and preserved systolic function (n = 36); and 3, RV enlargement and systolic dysfunction (n = 42). RESULTS: Patients had larger RA volume parameters and lower RA passive emptying fractions than controls (P< .01). The RA active emptying fraction was higher in patient groups 1 (mean ± SD, 45.5% ± 10.7%) and 2 (40.1% ± 4.0%) and lower in group 3 (19.3% ± 4.3%) compared to controls (35.4% ± 3.5%). The RA total emptying fraction was similar between groups 1 and 2 (59.3% ± 9.7% and 52.6% ± 3.4%, respectively) but was significantly lower in group 3 compared to controls (26.8% ± 5.1% versus 55.2% ± 5.1%). Right atrial volume and phasic function were substantially affected by RV structure and function. CONCLUSIONS: Real-time 3DE is a feasible, repeatable, and noninvasive method for accessing cyclic RA volume and function changes, such as those that occur with varying RV status in patients with pulmonary hypertension.

Left atrial asynchrony and mechanical function in patients with mitral stenosis before and immediately after percutaneous balloon mitral valvuloplasty: a real time three-dimensional echocardiography study.

OBJECTIVE: This study evaluated the feasibility of assessing left atrium (LA) function and asynchrony in patients with rheumatic mitral stenosis (MS) before and immediately after percutaneous balloon mitral valvuloplasty (PBMV) by real time three-dimensional echocardiography (RT3DE). METHODS: Thirty patients with rheumatic MS who underwent PBMV and 30 controls were enrolled. RT3DE was used to measure LA volume and function, the standard deviation of time to the minimal systolic volume divided into 16 segments, 12 segments, or 6 segments (Tmsv 16-SD, Tmsv 12-SD, Tmsv 6-SD), and the maximum differences (Tmsv 16-Dif, 12-Dif, 6-Dif) in RT3DE derived values in MS patients before and 2 days after PBMV were obtained and compared with those of normal controls. The associations between the LA asynchrony and heart volume, function, mitral valve area (MVA), maximum mitral valve gradient (MVGmax ), mean mitral valve gradient (MVGmean), and mean LA pressure (MLAP) were investigated. RESULTS: Left atrium asynchrony indexes were significantly larger, and LA function parameters were significantly lower in the MS group than in the controls (P < 0.05 for all). Of all the LA asynchrony indexes, LA Tmsv16-SD was most significantly correlated with the LA volume and function parameters, MVGmax , MVGmean , and MLAP (P < 0.05 for all). LA asynchrony indexes and LA volume significantly deceased, and LA function significantly increased post-PBMV (P < 0.05). CONCLUSION: Real time three-dimensional echocardiography is a reliable and reproducible method to quantify LA function and asynchrony. RT3DE revealed a significant, early improvement in LA function and asynchrony in MS patients after PBMV.