Integrated Antitumor Activities of Cellular Immunotherapy with CIK Lymphocytes and Interferons against KIT/PDGFRA Wild Type GIST

: Gastrointestinal stromal tumors (GISTs) are rare, mesenchymal tumors of the gastrointestinal tract, characterized by either KIT or PDGFRA mutation in about 85% of cases. KIT/PDGFRA wild type gastrointestinal stromal tumors (wtGIST) account for the remaining 15% of GIST and represent an unmet medical need: their prevalence and potential medical vulnerabilities are not completely defined, and effective therapeutic strategies are still lacking. In this study we set a patient-derived preclinical model of wtGIST to investigate their phenotypic features, along with their susceptibility to cellular immunotherapy with cytokine-induced killer lymphocytes (CIK) and interferons (IFN). We generated 11 wtGIST primary cell lines (wtGISTc). The main CIK ligands (MIC A/B; ULBPs), along with PD-L1/2, were expressed by wtGISTc and the expression of HLA-I molecules was preserved. Patient-derived CIK were capable of intense killing in vitro against wtGISTc resistant to both imatinib and sunitinib. We found that CIK produce a high level of granzyme B, IFNα and IFNγ. CIK-conditioned supernatant was responsible for part of the observed tumoricidal effect, along with positive bystander modulatory activities enhancing the expression of PD-L1/2 and HLA-I molecules. IFNα, but not In, had direct antitumor effects on 50% (4/8) of TKI-resistant wtGISTc, positively correlated with the tumor expression of IFN receptors. wtGIST cells that survived IFNα were still sensitive to CIK immunotherapy. Our data support the exploration of CIK immunotherapy in clinical studies for TKI-resistant wtGIST, proposing reevaluation for IFNα within this challenging setting

Designing all-graphene nanojunctions by covalent functionalization

We investigated theoretically the effect of covalent edge functionalization, with organic functional groups, on the electronic properties of graphene nanostructures and nano-junctions. Our analysis shows that functionalization can be designed to tune electron affinities and ionization potentials of graphene flakes, and to control the energy alignment of frontier orbitals in nanometer-wide graphene junctions. The stability of the proposed mechanism is discussed with respect to the functional groups, their number as well as the width of graphene nanostructures. The results of our work indicate that different level alignments can be obtained and engineered in order to realize stable all-graphene nanodevices

Enrichment of CD56dimKIR+CD57+ highly cytotoxic NK cells in tumor infiltrated lymph nodes of melanoma patients

An important checkpoint in the progression of melanoma is the metastasis to lymph nodes. Here, to investigate the role of lymph node NK cells in disease progression, we analyze frequency, phenotype and functions of NK cells from tumor-infiltrated (TILN) and tumor-free ipsilateral lymph nodes (TFLN) of the same patients. We show an expansion of CD56dimCD57dimCD69+CCR7+KIR+ NK cells in TILN. TILN NK cells display robust cytotoxic activity against autologous melanoma cells. In the blood of metastatic melanoma patients the frequency of NK cells expressing the receptors for CXCL8 receptor is increased compared to healthy subjects, and blood NK cells also express the receptors for CCL2 and IL6. These factors are produced in high amount in TILN and in vitro switch the phenotype of blood NK cells from healthy donors to the phenotype associated with TILN. Our data suggest that the microenvironment of TILN generates and/or recruits a particularly effective NK cell subset

Engineering dielectric materials for high-performance organic light emitting transistors (Olets)

Funding Information: The Author thanks the support from Academy of Finland Flagship Program (Grant No.: 320167, PREIN). Author thanks Gianluca Generali and many colleagues in ETC srl and CNR-ISMN (Italy) for valuable discussions on organic light emitting transistors during the years. Funding Information: Acknowledgments: The Author thanks the support from Academy of Finland Flagship Program (Grant No.: 320167, PREIN). Author thanks Gianluca Generali and many colleagues in ETC srl and CNR-ISMN (Italy) for valuable discussions on organic light emitting transistors during the years. Publisher Copyright: © 2021 by the author. Licensee MDPI, Basel, Switzerland.Organic light emitting transistors (OLETs) represent a relatively new technology platform in the field of optoelectronics. An OLET is a device with a two-fold functionality since it behaves as a thin-film transistor and at the same time can generate light under appropriate bias conditions. This Review focuses mainly on one of the building blocks of such device, namely the gate dielectrics, and how it is possible to engineer it to improve device properties and performances. While many findings on gate dielectrics can be easily applied to organic light emitting transistors, we here concentrate on how this layer can be exploited and engineered as an active tool for light manipulation in this novel class of optoelectronic devices.Peer reviewe

Carbon Nanotubes and Graphene Nanoribbons: Potentials for Nanoscale Electrical Interconnects

Carbon allotropes have generated much interest among different scientific communities due to their peculiar properties and potential applications in a variety of fields. Carbon nanotubes and more recently graphene have shown very interesting electrical properties along with the possibility of being grown and/or deposited at a desired location. In this Review, we will focus our attention on carbon-based nanostructures (in particular, carbon nanotubes and graphene nanoribbons) which could play an important role in the technological quest to replace copper/low-k for interconnect applications. We will provide the reader with a number of possible architectures, including single-wall as well as multi-wall carbon nanotubes, arranged in horizontal and vertical arrays, regarded as individual objects as well as bundles. Modification of their functional properties in order to fulfill interconnect applications requirements are also presented. Then, in the second part of the Review, recently discovered graphene and in particular graphene and few-graphene layers nanoribbons are introduced. Different architectures involving nanostructured carbon are presented and discussed in light of interconnect application in terms of length, chirality, edge configuration and more

High-k fluoropolymers dielectrics for low-bias ambipolar organic light emitting transistors (Olets)

Funding Information: Author Contributions: Conceptualization, A.A. and C.S.; methodology, A.A. and C.S.; validation, A.A., K.G.-R., and C.S.; data curation, A.A., K.G.-R., and C.S.; writing—original draft preparation, A.A. and C.S.; writing—review and editing, A.A., K.G.-R., and C.S.; supervision, C.S.; project administration, C.S.; funding acquisition, C.S. All authors have read and agreed to the published ver-sion ofFunding:the manuThescript.authors acknowledge the support from the Academy of Finland Flagship Program (Grant No.: 320167, PREIN) and the Aalto seed funding scheme. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.Organic light emitting transistors (OLETs) combine, in the same device, the function of an electrical switch with the capability of generating light under appropriate bias conditions. In this work, we demonstrate how engineering the dielectric layer based on high-k polyvinylidene fluoride (PVDF)-based polymers can lead to a drastic reduction of device driving voltages and the improvement of its optoelectronic properties. We first investigated the morphology and the dielectric response of these polymer dielectrics in terms of polymer (P(VDF-TrFE) and P(VDF-TrFE-CFE)) and solvent content (cyclopentanone, methylethylketone). Implementing these high-k PVDF-based dielectrics enabled low-bias ambipolar organic light emitting transistors, with reduced threshold voltages (<20 V) and enhanced light output (compared to conventional polymer reference), along with an overall improvement of the device efficiency. Further, we preliminary transferred these fluorinated high-k dielectric films onto a plastic substrate to enable flexible light emitting transistors. These findings hold potential for broader exploitation of the OLET platform, where the device can now be driven by commercially available electronics, thus enabling flexible low-bias organic electronic devices.Peer reviewe

TCTA:Ir(ppy)3 Green Emissive Blends in Organic Light-Emitting Transistors (OLETs)

Organic light-emitting transistors are photonic devices combining the function of an electrical switch with the capability of generating light under appropriate bias conditions. Achieving high-performance light-emitting transistors requires high-mobility organic semiconductors, optimized device structures, and highly efficient emissive layers. In this work, we studied the optoelectronic response of green blends (TCTA:Ir(ppy)3) with varying doping concentrations in the limit of field-effect within a transistor device configuration. Increasing the dye concentration within the blend leads to a quenching of the photoluminescence signal; however, when implemented in a multilayer stack in a transistor, we observed an approximately 5-fold improvement in the light output for a 10% Ir(ppy)3 doping blend. We analyzed our results in terms of balanced charge transport in the emissive layer, which, in the limit of field-effect (horizontal component), leads to an improved exciton formation and decay process. While the performances of our devices are yet to achieve the state-of-the-art diode counterpart, this work demonstrates that engineering the emissive layer is a promising approach to enhance the light emission in field-effect devices. This opens the way for a broader exploitation of organic light-emitting transistors as alternative photonic devices in several fields, ranging from display technology to flexible and wearable electronics.Peer reviewe

TCTA:Ir(ppy)₃ Green Emissive Blends in Organic Light-Emitting Transistors (OLETs)

Organic light-emitting transistors are photonic devices combining the function of an electrical switch with the capability of generating light under appropriate bias conditions. Achieving high-performance light-emitting transistors requires high-mobility organic semiconductors, optimized device structures, and highly efficient emissive layers. In this work, we studied the optoelectronic response of green blends (TCTA:Ir(ppy)3) with varying doping concentrations in the limit of field-effect within a transistor device configuration. Increasing the dye concentration within the blend leads to a quenching of the photoluminescence signal; however, when implemented in a multilayer stack in a transistor, we observed an approximately 5-fold improvement in the light output for a 10% Ir(ppy)3 doping blend. We analyzed our results in terms of balanced charge transport in the emissive layer, which, in the limit of field-effect (horizontal component), leads to an improved exciton formation and decay process. While the performances of our devices are yet to achieve the state-of-the-art diode counterpart, this work demonstrates that engineering the emissive layer is a promising approach to enhance the light emission in field-effect devices. This opens the way for a broader exploitation of organic light-emitting transistors as alternative photonic devices in several fields, ranging from display technology to flexible and wearable electronics

Highly Efficient Red Organic Light-Emitting Transistors (OLETs) on High‑<i>k</i> Dielectric

The investigation of the optoelectronic properties of a red organic light-emitting transistor using a high-<i>k</i> polymer (P­(VDF-TrFE-CFE)) as gate dielectric is reported. Introducing the high-<i>k</i> polymer strongly reduces the threshold voltages (compared to poly­(methyl methacrylate)) with improved efficiency, while maintaining comparable output light power. Use of a high-<i>k</i> polymer as gate dielectric enables the organic light-emitting transistor platform to be exploited in the display market, as it can be driven by commercially available electronics, thus enabling low-bias-driven organic electronics