The Interplay between T Cells and Cancer: The Basis of Immunotherapy.

Over the past decade, immunotherapy has emerged as one of the most promising approaches to cancer treatment. The use of immune checkpoint inhibitors has resulted in impressive and durable clinical responses in the treatment of various cancers. Additionally, immunotherapy utilizing chimeric antigen receptor (CAR)-engineered T cells has produced robust responses in blood cancers, and T cell receptor (TCR)-engineered T cells are showing promising results in the treatment of solid cancers. Despite these noteworthy advancements in cancer immunotherapy, numerous challenges remain. Some patient populations are unresponsive to immune checkpoint inhibitor therapy, and CAR T cell therapy has yet to show efficacy against solid cancers. In this review, we first discuss the significant role that T cells play in the body's defense against cancer. We then delve into the mechanisms behind the current challenges facing immunotherapy, starting with T cell exhaustion due to immune checkpoint upregulation and changes in the transcriptional and epigenetic landscapes of dysfunctional T cells. We then discuss cancer-cell-intrinsic characteristics, including molecular alterations in cancer cells and the immunosuppressive nature of the tumor microenvironment (TME), which collectively facilitate tumor cell proliferation, survival, metastasis, and immune evasion. Finally, we examine recent advancements in cancer immunotherapy, with a specific emphasis on T-cell-based treatments.

Distinct RBC alloantibody responses in type 1 interferon-dependent and -independent lupus mouse models.

During transfusion of red blood cells (RBCs), recipients are exposed to both ABO and non-ABO 'minor' antigens. RBC donor units and recipient RBCs are not routinely matched for non-ABO antigens. Thus, recipients are exposed to many RBC alloantigens that can lead to RBC alloantibody production and subsequent clinically significant hemolysis. RBC alloantibodies also significantly limit the provision of compatible RBC units for recipients. Prior studies indicate that the frequency of RBC alloimmunization is increased during inflammatory responses and in patients with autoimmune diseases. Still, mechanisms contributing to alloimmune responses in patients with autoimmunity are not well understood. More than half of adult patients with systemic lupus erythematosus (SLE) produce type 1 interferons (IFNα/ß) and express IFNα/ß stimulated genes (ISGs). Previously, we reported that IFNα/ß promote RBC alloimmune responses in the pristane mouse model, which develops a lupus-like phenotype that is dependent on IFNα/ß signaling. However, it is unclear whether IFNα/ß or the lupus-like phenotype induces alloimmunization in lupus models. Therefore, we tested the hypothesis that IFNα/ß promotes RBC alloimmune responses in lupus by examining alloimmune responses in IFNα/ß-independent (MRL-lpr) and IFNα/ß-dependent (pristane) lupus models. Whereas pristane treatment significantly induced interferon-stimulated genes (ISGs), MRL-lpr mice produced significantly lower levels that were comparable to levels in untreated WT mice. Transfusion of murine RBCs that express the KEL antigen led to anti-KEL IgG production by pristane-treated WT mice. However, MRL-lpr mice produced minimal levels of anti-KEL IgG. Treatment of MRL-lpr mice with recombinant IFNα significantly enhanced alloimmunization. Collectively, results indicate that a lupus-like phenotype in pre-clinical models is not sufficient to induce RBC alloantibody production, and IFNα/ß gene signatures may be responsible for RBC alloimmune responses in lupus mouse models. If these findings are extended to alternate pre-clinical models and clinical studies, patients with SLE who express an IFNα/ß gene signature may have an increased risk of developing RBC alloantibodies and may benefit from more personalized transfusion protocols.

GODoc: high-throughput protein function prediction using novel k-nearest-neighbor and voting algorithms.

BACKGROUND: Biological data has grown explosively with the advance of next-generation sequencing. However, annotating protein function with wet lab experiments is time-consuming. Fortunately, computational function prediction can help wet labs formulate biological hypotheses and prioritize experiments. Gene Ontology (GO) is a framework for unifying the representation of protein function in a hierarchical tree composed of GO terms. RESULTS: We propose GODoc, a general protein GO prediction framework based on sequence information which combines feature engineering, feature reduction, and a novel ​k​-nearest-neighbor algorithm to resolve the multiple GO prediction problem. Comprehensive evaluation on CAFA2 shows that GODoc performs better than two baseline models. In the CAFA3 competition (68 teams), GODoc ranks 10th in Cellular Component Ontology. Regarding the species-specific task, the proposed method ranks 10th and 8th in the eukaryotic Cellular Component Ontology and the prokaryotic Molecular Function Ontology, respectively. In the term-centric task, GODoc performs third and is tied for first for the biofilm formation of Pseudomonas aeruginosa and the long-term memory of Drosophila melanogaster, respectively. CONCLUSIONS: We have developed a novel and effective strategy to incorporate a training procedure into the k-nearest neighbor algorithm (instance-based learning) which is capable of solving the Gene Ontology multiple-label prediction problem, which is especially notable given the thousands of Gene Ontology terms.

Lead-free cesium tin halide nanocrystals for light-emitting diodes and color down conversion.

Organometal halide perovskites are attracting a great deal of attention because of their long carrier diffusion lengths, wide wavelength tunability, and narrow-band emission. However, the toxicity of lead has caused considerable environmental and health concerns. In this work, lead-free cesium tin halide nanocrystals are synthesized and investigated. CsSnBr3 and CsSnI3 nanocrystals, 25 and 7 nm in size, are synthesized by a facile hot injection method. Absorption spectroscopy, photoluminescence spectroscopy, and X-ray diffraction were used to understand their structural and optical properties. CsSnBr3 and CsSnI3 nanocrystals show emission peaks at 683 and 938 nm, respectively. These nanocrystals show shelf stability for a few months. Temperature-dependent photoluminescence is utilized to know more about fundamental physical parameters, such as exciton binding energy, charge carrier-phonon interactions and band gap. Light-emitting diodes and color down-conversion films are also demonstrated using these lead free perovskite nanocrystals.

Ultrastable, Deformable, and Stretchable Luminescent Organic-Inorganic Perovskite Nanocrystal-Polymer Composites for 3D Printing and White Light-Emitting Diodes.

Organic-inorganic perovskite nanocrystals with excellent optoelectronic properties have been utilized in various applications, despite their stability issues. The perovskite materials are sensitive to environments such as polar solvents, moisture, and heat. Thus, they are not used for extrusion three-dimensional (3D) printing, as it is usually conducted in the ambient environment and requires heating to liquefy the printed materials. In this work, 11 thermoplastic polymers conventionally used for extrusion 3D printing were investigated to test their capability as protective encapsulation materials for perovskite nanocrystals. Three of them exhibited good protective properties, and one (polycaprolactone, PCL) of these three could be blended with perovskite nanocrystals to form perovskite nanocrystal-PCL composites, which were deformable and stretchable once heated. Because of the low melting point of PCL, the perovskite nanocrystals maintained their optical properties after 3D printing, and the printed objects were still having fluorescent behavior. Moreover, fluorescent micrometer-sized fibers based on the perovskite nanocrystal-PCL composites could also be simply prepared using cotton candy makers. Perovskite nanocrystal-PCL composite films with different emission wavelengths were incorporated with blue light-emitting diodes (LEDs) to realize white LEDs with Commission Internationale de l'Éclairage chromaticity coordinates of (0.33, 0.33).

Efficient Low-Temperature Solution-Processed Lead-Free Perovskite Infrared Light-Emitting Diodes.

Lead-free perovskite infrared light-emitting diodes are achieved by using a halide perovskite CsSnI3 as an emissive layer. The film shows compact micrometer-sized grains with only a few pinholes and cracks at the grain boundaries. The device exhibits maximum radiance of 40 W sr-1 m-2 at a current density of 364.3 mA cm-2 and maximum external quantum efficiency of 3.8% at 4.5 V.