Purpose Immunomodulatory drugs differ in mechanism-of-action from directly cytotoxic cancer therapies. Identifying factors predicting clinical response could guide patient selection and therapeutic optimization. Experimental Design Patients (N=41) with melanoma, non-small cell lung carcinoma (NSCLC), renal cell carcinoma (RCC), colorectal carcinoma or castration-resistant prostate cancer were treated on an early phase trial of anti-PD-1 (nivolumab) at one institution and had evaluable pre-treatment tumor specimens. Immunoarchitectural features including PD-1, PD-L1, and PD-L2 expression, patterns of immune cell infiltration, and lymphocyte subpopulations, were assessed for interrelationships and potential correlations with clinical outcomes. Results Membranous (cell surface) PD-L1 expression by tumor cells and immune infiltrates varied significantly by tumor type and was most abundant in melanoma, NSCLC, and RCC. In the overall cohort, PD-L1 expression was geographically associated with infiltrating immune cells (p<0.001), although lymphocyte-rich regions were not always associated with PD-L1 expression. Expression of PD-L1 by tumor cells and immune infiltrates was significantly associated with expression of PD-1 on lymphocytes. PD-L2, the second ligand for PD-1, was associated with PD-L1 expression. Tumor cell PD-L1 expression correlated with objective response to anti-PD-1 therapy, when analyzing either the specimen obtained closest to therapy or the highest scoring sample among multiple biopsies from individual patients. These correlations were stronger than borderline associations of PD-1 expression or the presence of intratumoral immune cell infiltrates with response. Conclusions Tumor PD-L1 expression reflects an immune-active microenvironment and, while associated other immunosuppressive molecules including PD-1 and PD-L2, is the single factor most closely correlated with response to anti-PD-1 blockade.

Artificial van der Waals heterostructures with two-dimensional (2D) atomic crystals are promising as an active channel or as a buffer contact layer for next-generation devices. However, genuine 2D heterostructure devices remain limited because of impurity-involved transfer process and metastable and inhomogeneous heterostructure formation. We used laser-induced phase patterning, a polymorph engineering, to fabricate an ohmic heterophase homojunction between semiconducting hexagonal (2H) and metallic monoclinic (1T') molybdenum ditelluride (MoTe2) that is stable up to 300°C and increases the carrier mobility of the MoTe2 transistor by a factor of about 50, while retaining a high on/off current ratio of 10(6). In situ scanning transmission electron microscopy results combined with theoretical calculations reveal that the Te vacancy triggers the local phase transition in MoTe2, achieving a true 2D device with an ohmic contact.

Enhancer of zeste homolog 2 (EZH2) is a mammalian histone methyltransferase that contributes to the epigenetic silencing of target genes and that regulates the survival and metastasis of cancer cells. EZH2 is overexpressed in aggressive solid tumors by mechanisms that remain unclear. Here, we show that the expression and function of EZH2 in cancer cell lines is inhibited by microRNA-101 (miR-101). Analysis of human prostate tumors revealed that miR-101 expression decreases during cancer progression, paralleling an increase in EZH2 expression. One or both of the two genomic loci encoding miR-101 were somatically lost in 37.5% of clinically localized prostate cancers (6/16) and 66.7% of metastatic disease (22/33). We propose that genomic loss of miR-101 in cancer leads to overexpression of EZH2 and concomitant dysregulation of epigenetic pathways, resulting in cancer progression.Polycomb Group Proteins, including EZH2, play a master regulatory role in controlling important cellular process such as maintaining stem cell pluripotency (1-3), cell proliferation (4,5), early embryogenesis (6), and X chromosome inactivation (7). EZH2 functions in a multiprotein complex called Polycomb Repressive Complex 2 (PRC2) which includes SUZ12 (Suppressor of Zeste 12) and EED (Embryonic Ectoderm Development) (8,9). The primary activity of the EZH2 protein complex is to tri-methylate histone H3 lysine 27 (H3K27) at target gene promoters, leading to epigenetic silencing (10,11). Mounting evidence suggests that #Address correspondence and requests for reprints to:

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Two-dimensional (2D) transition metal oxide systems present exotic electronic properties and high specific surface areas, and also demonstrate promising applications ranging from electronics to energy storage. Yet, in contrast to other types of nanostructures, the question as to whether we could assemble 2D nanomaterials with an atomic thickness from molecules in a general way, which may give them some interesting properties such as those of graphene, still remains unresolved. Herein, we report a generalized and fundamental approach to molecular self-assembly synthesis of ultrathin 2D nanosheets of transition metal oxides by rationally employing lamellar reverse micelles. It is worth emphasizing that the synthesized crystallized ultrathin transition metal oxide nanosheets possess confined thickness, high specific surface area and chemically reactive facets, so that they could have promising applications in nanostructured electronics, photonics, sensors, and energy conversion and storage devices.

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Nanoporous carbon and nanoporous cobalt oxide (Co3O4) materials have been selectively prepared from a single metal-organic framework (MOF) (zeolitic imidazolate framework, ZIF-67) by optimizing the annealing conditions. The resulting ZIF-derived carbon possesses highly graphitic walls and a high specific surface area of 350 m(2)·g(-1), while the resulting ZIF-derived nanoporous Co3O4 possesses a high specific surface area of 148 m(2)·g(-1) with much less carbon content (1.7 at%). When nanoporous carbon and nanoporous Co3O4 were tested as electrode materials for supercapacitor application, they showed high capacitance values (272 and 504 F·g(-1), respectively, at a scan rate of 5 mV·s(-1)). To further demonstrate the advantages of our ZIF-derived nanoporous materials, symmetric (SSCs) and asymmetric supercapacitors (ASCs) were also fabricated using nanoporous carbon and nanoporous Co3O4 electrodes. Improved capacitance performance was successfully realized for the ASC (Co3O4//carbon), better than those of the SSCs based on nanoporous carbon and nanoporous Co3O4 materials (i.e., carbon//carbon and Co3O4//Co3O4). The developed ASC with an optimal mass loading can be operated within a wide potential window of 0.0-1.6 V, which leads to a high specific energy of 36 W·h·kg(-1). More interestingly, this ASC also exhibits excellent rate capability (with the highest specific power of 8000 W·kg(-1) at a specific energy of 15 W·h·kg(-1)) combined with long-term stability up to 2000 cycles.

The vanadium redox flow battery, which was first suggested by Skyllas -Kazacos and co-workers in 1985, is an electrochemical storage system which allows energy to be stored in two solutions containing different redox couples. Unlike commercially available batteries, all vanadium redox flow batteries have unique configurations, determined by the size of the electrolyte tanks. This technology has been proven to be an economically attractive and low-maintenance solution, with significant benefits over the other types of batteries. Moreover, the soaring demand for large-scale energy storage has, in turn, increased demands for unlimited capacity, design flexibility, and good safety systems. This work reviews and discusses the progress on electrodes their reaction mechanisms as key components of the vanadium redox flow battery over the past 30 years. In terms of future outlook, we also provide practical guidelines for the further development of self-sustaining electrodes for vanadium redox flow batteries as an attractive energy storage system.