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.

In situ growth of metal-organic framework thin films with gas sensing and molecule storage properties.

New porous metal-organic framework (MOF) films based on the flexible ligand 1,3,5-tris[4-(carboxyphenyl)oxamethyl]-2,4,6-trimethylbenzene (H3TBTC) were fabricated on α-Al2O3 substrates under solvent thermal conditions. The factors affecting the fabrication of films, such as the temperature of pre-activation and the dosage of the reagents, were investigated. Tuning the subtle factors on film fabrications, a series of MOF thin films with different morphologies and grain sizes were prepared. The morphology and grain size of the films are monitored by scanning electron microscopy (SEM). X-ray diffraction (XRD) and attenuated total reflection infrared (ATR-IR) were also used to characterize the MOF films. The results indicate that the temperature of pre-activation and the dosage of the reagents are the key parameters during the process of film formation. The properties of the films, especially the sensing and sorption behavior, have been studied by an optical digital cameral and ultraviolet-visible (UV-vis) spectra. The evidence shows that the films are sensitive to small organic molecules, such as methanol and pyridine. Meanwhile, the films can adsorb small dye molecules. Thus, the films may have potential applications in either organic vapor sensing or storage of small dye molecules.

Top-Down Synthesis of Nanostructured Platinum-Lanthanide Alloy Oxygen Reduction Reaction Catalysts: Pt xPr/C as an Example.

The oxygen reduction reaction (ORR) is of great interest for future sustainable energy conversion and storage, especially concerning fuel cell applications. The preparation of active, affordable, and scalable electrocatalysts and their application in fuel cell engines of hydrogen cars is a prominent step toward the reduction of air pollution, especially in urban areas. Alloying nanostructured Pt with lanthanides is a promising approach to enhance its catalytic ORR activity, whereby the development of a simple synthetic route turned out to be a nontrivial endeavor. Herein, for the first time, we present a successful single-step, scalable top-down synthetic route for Pt-lanthanide alloy nanoparticles, as witnessed by the example of Pr-alloyed Pt nanoparticles. The catalyst was characterized by high-resolution transmission electron microscopy, energy-dispersive X-ray spectroscopy, X-ray diffraction, and photoelectron spectroscopy, and its electrocatalytic oxygen reduction activity was investigated using a rotating disk electrode technique. Pt xPr/C showed ∼3.5 times higher [1.96 mA/cm2Pt, 0.9 V vs reversible hydrogen electrode (RHE)] specific activity and ∼1.7 times higher (0.7 A/mgPt, 0.9 V vs RHE) mass activity compared to commercial Pt/C catalysts. On the basis of previous findings and characterization of the Pt xPr/C catalyst, the activity improvement over commercial Pt/C originates from a lattice strain introduced by the alloying process.

Integration of metal-organic frameworks into an electrochemical dielectric thin film for electronic applications.

The integration of porous metal-organic frameworks onto the surface of materials, for use as functional devices, is currently emerging as a promising approach for gas sensing and flexible displays. However, research focused on potential applications in electronic devices is in its infancy. Here we present a facile strategy by which interpenetrated, crystalline metal-organic framework films are deposited onto conductive metal-plate anodes via in situ temperature-controlled electrochemical assembly. The nanostructure of the surface as well as the thickness and uniformity of the film are well controlled. More importantly, the resulting films exhibit enhanced dielectric properties compared to traditional inorganic or organic gate dielectrics. This study demonstrates the successful implementation of the rational design of metal-organic framework thin films on conductive supports with high-performance dielectric properties.

Patterned growth of luminescent metal-organic framework films: a versatile electrochemically-assisted microwave deposition method.

Electrochemically-assisted microwave deposition technology, a facile method for the fabrication of luminescent metal-organic framework (LMOF) films, is presented herein. This method was further developed into a versatile method for preparing patterned LMOF films. The strategy based on this method can spatially locate microcrystals of MOFs on a surface, which provides great promise in anti-counterfeiting barcode applications.

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.

Functionally distinct subsets of CD4⁺ regulatory T cells in patients with laryngeal squamous cell carcinoma are indicative of immune deregulation and disease progression.

CD4+ regulatory T cells (Tregs) mediate immune tolerance in laryngeal squamous cell carcinoma (LSCC). However, Tregs are functionally heterogeneous. Recently, we reported that three distinct Treg subsets (resting Tregs, activated Tregs and cytokine-secreting CD45RA-Foxp3lowCD4+ T cells) vary in the peripheral circulation of patients with head and neck squamous cell carcinoma (HNSCC); however, the potential implication of these Treg subsets in LSCC immunity is unclear. Here, we report that activated Tregs and cytokine­secreting CD45RA-Foxp3lowCD4+ T cells were increased in LSCC patients compared with healthy donors (HD) (p<0.001, p<0.001), whereas resting Tregs were decreased (p<0.001). Activated Tregs inhibited the proliferation of CD4+CD25- T cells (p<0.001) and secreted lower levels of interleukin-2 (p<0.001), interferon-γ (p<0.001) and tumor necrosis factor-α (p<0.001) compared with the cytokine-secreting CD45RA-Foxp3lowCD4+ T cells. Importantly, activated Treg prevalence was correlated with tumor stage (p=0.001) and nodal status (p=0.007). The prevalence of naïve CD4+ (p<0.001), naïve CD8+ (p=0.002), and Th1 T-cell subsets (p<0.001, p<0.001) was decreased in the LSCC patients. In conclusion, our findings showed that activated Tregs with suppressive activity are a distinct subset of Tregs in LSCC, and correlate with disease progression. Several immune system abnormalities in LSCC patients are represented by expansion of functionally activated Tregs, both in the circulation and tumor microenvironment along with decreased frequencies of naïve T-cell populations and Th1-cell populations.

CD45RA-Foxp3high but not CD45RA+Foxp3low suppressive T regulatory cells increased in the peripheral circulation of patients with head and neck squamous cell carcinoma and correlated with tumor progression.

BACKGROUND: T regulatory cells (Tregs) contribute to the progression of head and neck squamous cell carcinoma (HNSCC) by suppressing antitumor immunity. However, little is known regarding the functional heterogeneity of Tregs in HNSCC patients. METHODS: Using multicolor flow cytometry, the frequency of three Treg subsets, separated on the basis of CD45RA and Foxp3, from the peripheral circulation of newly-presenting HNSCC patients (19 oral cavity squamous cell carcinoma, 20 hypopharyngeal squamous cell carcinoma, 18 nasopharyngeal squamous cell carcinoma, 19 oropharyngeal squamous cell carcinoma, and 36 laryngeal squamous cell carcinoma) were assessed with regard to 31 healthy donors and clinicopathological features. Moreover, the functional capacity of each Treg subsets was evaluated based on CD45RA and CD25 expression. RESULTS: The frequency of Tregs in the peripheral circulation of HNSCC patients as a whole cohort was higher than in healthy donors (P < 0.0001). However, the frequency of Tregs was similar between patients with oral cavity squamous cell carcinoma and healthy donors (P = 0.269). Further dividing Tregs into three subsets based on Foxp3 and CD45RA expression revealed that the frequency of CD45RA-Foxp3high Tregs and CD45RA-Foxp3lowCD4+ T cells in patients with HNSCC developing from different subsites was higher than in healthy donors (P < 0.0001, P < 0.0001), whereas the frequency of CD45RA+Foxp3low Tregs was lower than in healthy donors (P < 0.0001). Functionally study revealed that CD45RA-CD25+++ Tregs significantly inhibit the proliferation of CD4+CD25- T cells (P < 0.001) and secrete lower levels of cytokines (P < 0.01) compared with CD45RA-CD25++CD4+ T cells. Importantly, the frequency of CD45RA-Foxp3high Tregs positively correlate with tumor stage (P < 0.0001) and nodal status (P < 0.0001). CONCLUSIONS: CD45RA-Foxp3high Tregs increase in the peripheral circulation of HNSCC patients, and correlate with tumor stage and nodal status; suggesting a role in tumor progression which may be manipulated by future immunotherapy.

Reversible crystal-to-amorphous-to-crystal phase transition and a large magnetocaloric effect in a spongelike metal organic framework material.

Reversible crystal-to-amorphous-to-crystal phase transition accompanied by changes in magnetic and NLO properties was first observed in a rigid non-porous spongelike MOF material. The crystal phase exhibits a high magnetocaloric effect, while the amorphous phase has potential application as a magnetic DMF sensor.