A positive-feedback loop between tumour infiltrating activated Treg cells and type 2-skewed macrophages is essential for progression of laryngeal squamous cell carcinoma.

BACKGROUND: Foxp3+ regulatory T (Treg) cells and M2 macrophages are associated with increased tumour progression. However, the interaction between Treg cells and M2 macrophages remains unclear. METHODS: The expression of FoxP3 and CD163 was detected by immunohistochemistry in 65 cases of laryngeal squamous cell carcinoma (LSCC). In vitro, the generation of activated Treg (aTreg) cells and M2 macrophages by interactions with their precursor cells were analysed by flow cytometry and ELISA. In vivo, the antitumour effects were assessed by combined targeting aTreg cells and M2 macrophages, and intratumoural immunocytes were analysed by flow cytometry. RESULTS: In LSCC tissue, accumulation of aTreg cells and M2 macrophages predicted a poor prognosis and were positively associated with each other. In vitro, aTreg cells were induced from CD4+CD25- T cells by cancer cell-activated M2-like macrophages. Consequently, these aTreg cells skewed the differentiation of monocytes towards an M2-like phenotype, thereby forming a positive-feedback loop. Combined targeting aTreg cells and M2 macrophages led to potent antitumour immunity in vivo. CONCLUSIONS: The positive-feedback loop between aTreg cells and M2 macrophages is essential to maintain or promote immunosuppression in the tumour microenvironment and may be a potential therapeutic target to inhibit tumour progression.

A dose optimization method of disinfection units and synergistic effects of combined disinfection in pilot tests.

The increasing requirement for reclaimed water has made it necessary to utilize multiple disinfection processes for efficient removal of organoleptic indicators, while guaranteeing microbial safety. However, there is not a proper way to appropriately distribute the operation load between different disinfection units. This study provides a new method to optimize doses of sequential ozonation, ultraviolet (UV) irradiation and chlorine disinfection units, and investigates the synergistic effects of combined disinfection on the basis of pilot tests. In this method, the minimal ozone dose is determined first for the removal of colority. The chlorine dose is then adjusted according to the required residual chlorine. At last, since it has few side effects and relatively low operating costs, UV dose is determined by the remaining requirement of microbial indicator reduction. By this method, the effluent of disinfection could meet the discharge standards of colority, residual chlorine, and microbial indicators. The operating cost was reduced by 48.7%, mainly by lowering the ozone dosage. The production of disinfection by-products (DBPs) was effectively controlled by decreasing the chlorine dosage compared with the original working conditions in the plant. Moreover, ozone pretreatment effectively improved the coliform inactivation efficiency of chlorine, and the combined disinfection method alleviated the tailing phenomenon and achieved a higher maximum log reduction of coliforms. The proposed method can help water reclamation plants reasonably determine operational loads between disinfection units with low cost and guaranteed performance.

[Spatial Variation and Potential Sources of Microplastics in Rivers in Tongzhou District, Beijing].

Microplastics are emerging contaminants, which can also absorb other contaminants, threatening the health of river ecosystems. However, research on the pollution of microplastics in rivers in northern China is still lacking. In this study, based on the sampling and analysis of water samples in 19 sites in six rivers in Tongzhou district, Beijing, the composition, spatial variation, and potential sources of microplastics were explored. The results showed that all sites were contaminated by microplastics, and the abundance of microplastics in the Xiaozhong River was the highest among all sites (3.50×104 n·m-3), which was 4.04 times that in the Yunchaojian River. The proportion of microplastics with particle sizes smaller than 2000 µm was 90.49%, and microplastics with particle sizes larger than 4000 µm were only found in two out of 19 sampling sites. The microplastics were fiber, film, fragment, and granule shaped. The proportion of fiber microplastics was the highest (90.23%) among all shapes. Most (84.29%) of the microplastics were transparent and blue. Rayon was the most common microplastic in each site, and its proportion in each site was over 66.67%. The proportions of other types of microplastics differed largely among different sites. Spatially, the abundance and types of microplastics in the upper reaches were higher than those in the lower reaches. According to spatial variations in shapes, types, colors, and abundance of microplastics, the potential sources of microplastics were identified. The potential sources of fiber microplastics were washing clothing and using fishing gear and dust-proof nets.

Comprehensive analysis of ferritin subunits expression and positive correlations with tumor-associated macrophages and T regulatory cells infiltration in most solid tumors.

Ferritin is the most important iron storage form and is known to influence tumor immunity. We previously showed that expression of ferritin light chain (FTL) and ferritin heavy chain (FTH1) subunits is increased in head and neck squamous cell carcinoma (HNSC). Here, we analyzed solid tumor datasets from The Cancer Genome Atlas and Genotype-Tissue Expression databases to investigate correlations between FTL and FTH1 expressions and (i) patient survival, using univariate, multivariate, Kaplan-Meier and Receiver Operator Characteristic analysis; and (ii) tumor-infiltrating immune cell subsets, using the bioinformatics tools Estimation of Stomal and Immune cells in Malignant Tumor tissues, Microenvironment Cell Population-counter, Tumor Immune Estimation Resource, and Tumor Immunology Miner. We found that FTL and FTH1 are upregulated and downregulated, respectively, in most of the human cancers analyzed. Tumor FTL levels were associated with prognosis in patients with lower grade glioma (LGG), whereas FTH1 levels were associated with prognosis in patients with liver hepatocellular carcinoma, HNSC, LGG, and kidney renal papillary cell carcinoma. In many cancers, FTL and FTH1 levels was significantly positively correlated with tumor infiltration by tumor-associated macrophages and T regulatory cells. These results suggest an important role for FTL and FTH1 in regulating tumor immunity to solid cancers.

Different prognoses in patients with profound sudden sensorineural hearing loss.

Background: Inner ear hemorrhage is increasingly recognized as a cochlear lesion that can cause profound sudden sensorineural hearing loss (SSNHL). Objectives: To investigate changes of cochlear and vestibular function and to compare therapeutic recovery from profound SSNHL induced by different etiologies. Material and methods: Eighty patients with profound SSNHL (≥90 dB) were divided into an inner ear hemorrhage group and a non-inner ear hemorrhage group by MRI. Statistical analysis was performed to compare the therapeutic effects from vertigo and hearing loss and the outcomes of follow-up in the two groups. Results: There were significant differences between the two groups in terms of the overall 14-day therapeutic response rate (20 vs. 48%), the incidence of imbalance (26.7 vs. 6%), the incidence of semicircular canal dysfunction on the affected side (60 vs. 20%), the incidence of abnormal C-VEMP and O-VEMP on the affected side (63.3 vs. 38%; and 60 vs. 30%, respectively), the average hearing threshold (74.2 ± 10.7 vs. 53.6 ± 11.4 dB), and the word recognition score (65.5 ± 21.7 vs. 83.5 ± 24.5%) at a 12-month follow-up. Conclusions and significance: A higher percentage of patients with profound SSNHL induced by inner ear hemorrhage were associated with vertigo and had a poor prognosis.

Epigoitrin, an Alkaloid From Isatis indigotica, Reduces H1N1 Infection in Stress-Induced Susceptible Model in vivo and in vitro.

Stress has been proven to modulate an individual's immune system through the release of pituitary and adrenal hormones such as the catecholamines, growth hormone, and glucocorticoids. These signal molecules can significantly alter the host immune system and make it susceptible to viral infection. In this study, we investigate whether epigoitrin, a natural alkaloid from Isatis indigotica, provides protection against influenza infection by reducing the host's susceptibility to influenza virus under stress and its underlying mechanism. To support it, the mouse restraint stress model and the corticosterone-induced stress model were employed. Our results demonstrated that epigoitrin significantly decreased the susceptibility of restraint mice to influenza virus, evidenced by lowered mortality, attenuated inflammation, and decreased viral replications in lungs. Further results revealed that epigoitrin reduced the protein expression of mitofusin-2 (MFN2), which elevated mitochondria antiviral signaling (MAVS) protein expression and subsequently increased the production of IFN-ß and interferon inducible transmembrane 3 (IFITM3), thereby helping to fight viral infections. In conclusion, our study indicated that epigoitrin could reduce the susceptibility to influenza virus via mitochondrial antiviral signaling.

Adoptive cell therapy of tolerogenic dendritic cells as inducer of regulatory T cells in allergic rhinitis.

BACKGROUND: Regulatory T cells (Tregs) have become promising candidates for immunotherapy in allergic rhinitis (AR). The contributing role of tolerogenic dendritic cells (tDCs) in the augmentation of Tregs in AR remains to be determined. METHODS: The properties of tDCs in expanding Tregs and their potential to ameliorate AR were evaluated in vitro and in vivo. RESULTS: Monocyte-derived tDCs stimulated with Dermatophagoides pteronyssinus allergen 1 favored the generation of activated Tregs (aTregs) and suppressed effector T-cell responses in a transforming growth factor-beta/interleukin-10 (TGF-ß/IL-10)-dependent manner in vitro. The adoptive transfer of tDCs inhibited allergic airway inflammation in the mouse model, whereas depletion of CD25+ cells or blocking TGF-ß/IL-10 signaling eliminated the inhibitory effect, indicating that Tregs were involved in the anti-inflammatory activity of tDCs. CONCLUSION: Our data show that tDCs are a potential therapeutic target in AR.

Eliciting cytotoxic T lymphocytes against human laryngeal cancer-derived antigens: evaluation of dendritic cells pulsed with a heat-treated tumor lysate and other antigen-loading strategies for dendritic-cell-based vaccination.

BACKGROUND: Dendritic cells (DCs) have been used successfully in clinical pilot studies. However, tumor-specific immunity and clinical responses were only induced in certain cancer patients. It has been well documented that immunotherapy efficacy can be optimized for responses using antigen pulsing. METHODS: The human laryngeal squamous cell cancer (LSCC) cell line SNU899 was used to evaluate the in vitro anti-tumor efficacy of three different preparations of dendritic cell (DC) vaccines consisting of either whole tumor cells or their derivatives including: i) DCs pulsed with a tumor cell supernatant (DC-TCS), ii) DCs pulsed with whole-cell tumor stressed lysate (DC-TSL), and iii) DCs pulsed with irradiated tumor cells (DC-ITC). RESULTS: Our results showed that DC-TSL is an effective source of tumor-associated antigens (TAAs) for pulsing DCs. DC-TSL induced the highest expansion of TAA-specific T cells, the strongest Th1 cytokine response, and the most potent cytotoxic T lymphocyte (CTL) activity. DC-TCS and DC-ITC inhibited T cell activation but induced a certain extent of CTL activity. CONCLUSIONS: These data suggest that DC-TSL is a more potent inducer of antitumor immunity against laryngeal cancer than other antigen-loading strategies using whole tumor cell materials. This strategy provides an alternative approach for DC-based immunotherapy for laryngeal cancer.

Blockade of MCP-1/CCR4 signaling-induced recruitment of activated regulatory cells evokes an antitumor immune response in head and neck squamous cell carcinoma.

FoxP3+ regulatory T (Treg) cells have diverse functions in the suppression of antitumor immunity. We show that FoxP3hiCD45RA-CD4+ Treg cells [activated Treg (aTreg) cells] are the predominant cell population among tumor-infiltrating FoxP3+ T cells, and that high aTreg cell-infiltrating content is associated with reduced survival in patients with head and neck squamous cell carcinoma (HNSCC). In vitro studies have demonstrated that aTreg cells can suppress tumor-associated antigen (TAA) effector T cell immune responses in HNSCC. Moreover, C-C chemokine receptor 4 (CCR4) was specifically expressed by aTreg cells in the peripheral blood of HNSCC patients. Using a RayBiotech human chemokine antibody array, we showed that monocyte chemoattractant protein-1 (MCP-1), an endogenous CCR4-binding ligand, was specifically upregulated in the HNSCC microenvironment compared to the other four CCR4-binding ligands. Blocking MCP-1/CCR4 signaling-induced aTreg cell recruitment using a CCR4 antagonist evoked antitumor immunity in mice, and lead to inhibition of tumor growth and prolonged survival. Therefore, blocking aTreg cell trafficking in tumors using CCR4-binding agents may be an effective immunotherapy for HNSCC.

Treatment and Prognosis of Anaplastic Thyroid Carcinoma: A Clinical Study of 50 Cases.

INTRODUCTION: Although anaplastic thyroid carcinoma (ATC) is rare, it is one of the most aggressive human cancers. The optimal multimodal therapy policy of ATC is still debated, and a standardized treatment strategy remains to be established. This study aimed to evaluate the management aspect and prognosis of ATC. MATERIALS AND METHODS: The data were analyzed retrospectively for 50 patients with ATC to evaluate the clinical characters, management and factors influencing survival. Survival analysis was performed by Kaplan-Merier method and log-rank test, and multivariate analysis was performed using Cox proportional hazard model. RESULTS: The 1-year and 2-year overall survival rates (OS) were 48.0% and 26.0% respectively in all patients, with the 2-year OS of 40.0% and 31.0% and 6.3% for stage IVA, IVB and IVC respectively (P <0.05). In stage IVA and IVB patients, combined surgery with radiotherapy improved overall survival, and the 2-year OS were 50.0% and 35.7% respectively in the group with combined surgery with radiotherapy and the group with surgery with only (P <0.05). Postoperative radiotherapy improved local control rate in stage IVA and IVB patients (P <0.05). However, surgery, radiotherapy or chemotherapy could not improve the survival of stage IVC patients. Multivariate analysis showed that distant metastases, surgery, radiotherapy and tumor residue could predict the prognosis. CONCLUSION: Combined surgery and radiotherapy could improve overall survival in stage IVA and IVB patients. Patients with ATC have a bad prognosis. Distant metastases, surgery, radiotherapy and tumor residue are the most important factors affecting the prognosis.