Basic Science and Pathogenesis.

Background: Abnormal brain inflammation is an important feature of Alzheimer's disease (AD). Central nervous system (CNS) inflammation is highly related to immune cell activation. Homeostasis of immune cell activity regulation is crucial for CNS autoimmune response.

A change of PD-1/PD-L1 expression on peripheral T cell subsets correlates with the different stages of Alzheimer's Disease.

Background: Immune checkpoints are a set of costimulatory and inhibitory molecules that maintain self-tolerance and regulate immune homeostasis. The expression of immune checkpoints on T cells in malignancy, chronic inflammation, and neurodegenerative diseases has gained increasing attention.

Results: To characterize immune checkpoints in neurodegenerative diseases, we aimed to examine the expression of the immune checkpoint PD-1/PD-L1 in peripheral T cells in different Alzheimer's disease (AD) patients.

Artificial Antigen Presentosomes for T Cell Activation.

CD8 T cells constitute an essential component of the adaptive immune system. They are activated through T cell receptor (TCR) recognizing antigenic peptides presented by MHC class I molecules expressed by antigen-presenting cells, such as dendritic cells (DCs). Harvesting a large number of activated, antigen-specific human CD8 T cells for functional studies has been a laborious task for immunologists, largely because of the variables associated with DC preparations.

The Impact of the Epigenetic Cancer Drug Azacitidine on Host Immunity: The Role of Myelosuppression, Iron Overload and tp53 Mutations in a Zebrafish Model.

The unsatisfactory real-world efficacy of the hypomethylating agent azacitidine in treating myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) has prompted us to investigate the hematological adverse events and host variables that may compromise the use of this epigenetic drug. Using the zebrafish, we found that azacitidine destroyed their myeloid precursors and impaired myeloid function by inhibiting antigen processing, allogeneic response and phagocytic activity, resulting in increased susceptibility to infection even by the normal flora E. coli.

Correction: Targeting a ribonucleoprotein complex containing the caprin-1 protein and the c-Myc mRNA suppresses tumor growth in mice: an identification of a novel oncotarget.

[This corrects the article DOI: 10.18632/oncotarget.3236.

Total HLA Class I Antigen Loss with the Downregulation of Antigen-Processing Machinery Components in Two Newly Established Sarcomatoid Hepatocellular Carcinoma Cell Lines.

Limited information is currently available concerning HLA class I antigen abnormalities in sarcomatoid hepatocellular carcinoma (sHCC). Here, we have analyzed the growth characteristics and HLA class I antigen status of four sHCC cell lines (sHCC29, sHCC63, sHCC74, and SAR-HCV); the first three were newly established in this study. Among the four, sHCC29 showed the highest growth rate and tumorigenicity in NOD-SCID mice.

Persistently elevated soluble MHC class I polypeptide-related sequence A and transforming growth factor-β1 levels are poor prognostic factors in head and neck squamous cell carcinoma after definitive chemoradiotherapy.

We evaluated the prognostic significance of immunologic inhibitory biomarkers in head and neck squamous cell carcinoma (HNSCC) patients undergoing definitive chemoradiotherapy (CRT). Thirty patients were prospectively enrolled. Plasma levels of soluble MHC class I polypeptide-related sequence A (sMICA) and transforming growth factor-β1 (TGF-β1) were measured before and 2 weeks after CRT.

Cytokeratin-8 in Anaplastic Thyroid Carcinoma: More Than a Simple Structural Cytoskeletal Protein.

Anaplastic thyroid carcinoma (ATC) is almost universally fatal. Elevated keratin-8 (KRT8) protein expression is an established diagnostic cancer biomarker in several epithelial cancers (but not ATC). Several keratins, including KRT8, have been suggested to have a role in cell biology beyond that of structural cytoskeletal proteins.

High-performance and high-sensitivity applications of graphene transistors with self-assembled monolayers.

Charge impurities and polar molecules on the surface of dielectric substrates has long been a critical obstacle to using graphene for its niche applications that involve graphene's high mobility and high sensitivity nature. Self-assembled monolayers (SAMs) have been found to effectively reduce the impact of long-range scatterings induced by the external charges. Yet, demonstrations of scalable device applications using the SAMs technique remains missing due to the difficulties in the device fabrication arising from the strong surface tension of the modified dielectric environment.

Multiple structural and epigenetic defects in the human leukocyte antigen class I antigen presentation pathway in a recurrent metastatic melanoma following immunotherapy.

Scant information is available about the molecular basis of multiple HLA class I antigen-processing machinery defects in malignant cells, although this information contributes to our understanding of the molecular immunoescape mechanisms utilized by tumor cells and may suggest strategies to counteract them. In the present study we reveal a combination of IFN-γ-irreversible structural and epigenetic defects in HLA class I antigen-processing machinery in a recurrent melanoma metastasis after immunotherapy. These defects include loss of tapasin and one HLA haplotype as well as selective silencing of HLA-A3 gene responsiveness to IFN-γ.

Targeting a ribonucleoprotein complex containing the caprin-1 protein and the c-Myc mRNA suppresses tumor growth in mice: an identification of a novel oncotarget.

Tylophorine compounds have been the focus of drug development for decades. Tylophorine derivatives exhibit anti-cancer activities but their cellular targets remain unknown. We used a biotinylated tylophorine derivative to probe for the interacting cellular target(s) of tylophorine.

Cytokeratin 8-MHC class I interactions: a potential novel immune escape phenotype by a lymph node metastatic carcinoma cell line.

Defective human leukocyte antigen (HLA) class I expression in malignant cells facilitates their escape from destruction by CD8(+) cytotoxic T lymphocytes. In this study, a post-translational mechanism of HLA class I abnormality that does not involve defects in the HLA subunits and antigen processing machinery components was identified and characterized. The marked HLA class I downregulation phenotype of a metastatic carcinoma cell line can be readily reversed by trypsin, suggesting a masking effect by serine protease-sensitive HLA class I-interacting factors.

Selective modulation of MHC class II chaperons by a novel IFN-γ-inducible class II transactivator variant in lung adenocarcinoma A549 cells.

Class II transactivator (CIITA) plays a critical role in controlling major histocompatibility complex (MHC) class II gene expression. In this study, two novel alternatively spliced variants of human interferon (IFN)-γ-inducible CIITA, one missing exon 7 (CIITAΔE7), the other with TAG inserted at exon 4/5 junction (CIITA-TAG), were identified and characterized. Both variants are naturally occurring since they are present in primary cells.

Adaptive immune responses elicited by baculovirus and impacts on subsequent transgene expression in vivo.

Baculovirus (BV) is a promising gene therapy vector and typically requires readministration because BV mediates transient expression. However, how the prime-boost regimen triggers BV-specific adaptive responses and their impacts on BV readministration, transgene expression, and therapeutic/vaccine efficacy remain unknown. Here we unraveled that BV injection into BALB/c mice induced the production of BV-specific antibodies, including IgG1 and IgG2a, which could neutralize BV by antagonizing the envelope protein gp64 and impede BV-mediated transgene expression.

An RSVM based two-teachers-one-student semi-supervised learning algorithm.

Based on the reduced SVM, we propose a multi-view algorithm, two-teachers-one-student, for semi-supervised learning. With RSVM, different from typical multi-view methods, reduced sets suggest different views in the represented kernel feature space rather than in the input space. No label information is necessary when we select reduced sets, and this makes applying RSVM to SSL possible.

Use of nakagami statistics and empirical mode decomposition for ultrasound tissue characterization by a nonfocused transducer.

The Nakagami parameter associated with the Nakagami distribution estimated from ultrasonic backscattered signals reflects the scatterer concentration in a tissue. A nonfocused transducer does not allow tissue characterization based on the Nakagami parameter. This paper proposes a new method called the noise-assisted Nakagami parameter based on empirical mode decomposition of noisy backscattered echoes to allow quantification of the scatterer concentration based on data obtained using a nonfocused transducer.

An adaptive threshold filter for ultrasound signal rejection.

The threshold filter is a frequently used technique in ultrasound B-scan to reject the small echoes contributed from backscattering that blur the tissue interface and reduce the image contrast. Note that using the threshold based on one value would simultaneously destroy local waveform features of the reflection echoes with amplitudes larger than threshold value. To resolve this problem, we developed an adaptive threshold filter based on the noise-assisted empirical mode decomposition (EMD).

Incremental forward feature selection with application to microarray gene expression data.

In this study, the authors propose a new feature selection scheme, the incremental forward feature selection, which is inspired by incremental reduced support vector machines. In their method, a new feature is added into the current selected feature subset if it will bring in the most extra information. This information is measured by using the distance between the new feature vector and the column space spanned by current feature subset.

Total HLA class I loss in a sarcomatoid renal carcinoma cell line caused by the coexistence of distinct mutations in the two encoding beta2-microglobulin genes.

In renal cell carcinoma (RCC), HLA class I downregulation has been found in about 40% of the lesions examined. Since only scanty information is available about the molecular basis of these defects, we have investigated the mechanism(s) underlying HLA class I antigen downregulation or loss in six RCC cell lines. Five of them express HLA class I antigens although at various levels; on the other hand, HLA class I antigens are not detectable on the remaining cell line, the RCC52 cell line, belonging to a sarcomatoid subtype, even following incubation with IFN-gamma.

Cellular co-localization of intron-4 containing mRNA and HLA-G soluble protein in melanoma analyzed by fluorescence in situ hybridization.

HLA-G5, -G6, and -G7 soluble isoforms of the immunosuppressive HLA-G molecule are produced from the splice variants of the primary HLA-G mRNA transcript containing intron-4 that encodes a specific 21 amino acids tail. In particular, HLA-G5 interacts with the inhibitory ILT2/4 and KIR2DL4 receptors that are expressed on immune cells. Acquisition of soluble HLA-G in the microenvironment may turn a HLA-G non-expressing cell into a HLA-G-bearing one.

Arterial pulse waveform analysis by the probability distribution of amplitude.

Augmentation index (AIx) calculated from the pressure waveform of an artery is widely used to quantify the arterial stiffness and evaluate the cardiovascular risk. The key for calculating AIx is to locate the inflection point on the waveform signal, which is caused by the wave reflection. This study applies the probability distribution of the pressure waveform to identify the inflection point for estimating AIx.

NK cell activating ligands on human malignant cells: molecular and functional defects and potential clinical relevance.

Malignant transformation of cells is frequently associated with HLA class I antigen downregulation or loss. This abnormality provides malignant cells with a mechanism to escape control by HLA class I antigen-restricted, tumor antigen-specific cytotoxic T lymphocytes. Surprisingly, HLA class I antigen downregulation or loss by tumor cells is not associated with control of tumor growth by natural killer (NK) cells, as it would be predicted by the "missing-self" hypothesis.

Immune selective pressure and HLA class I antigen defects in malignant lesions.

The revived cancer immune surveillance theory has emphasized the active role the immune system plays in eliminating tumor cells and in facilitating the emergence of their immunoresistant variants. MHC class I molecule abnormalities represent, at least in part, the molecular phenotype of these escape variants, given the crucial role of MHC class I molecules in eliciting tumor antigen-specific T cell responses, the high frequency of HLA class I antigen abnormalities in malignant lesions and their association with a poor clinical course of the disease. Here, we present evidence for this possibility and review the potential mechanisms by which T cell selective pressure participates in the generation of tumor cells with MHC class I molecule defects.

Defective human leukocyte antigen class I-associated antigen presentation caused by a novel beta2-microglobulin loss-of-function in melanoma cells.

The major histocompatibility complex class I molecules consist of three subunits, the 45-kDa heavy chain, the 12-kDa beta(2)-microglobulin (beta(2)m), and an approximately 8-9-residue antigenic peptide. Without beta(2)m, the major histocompatibility complex class I molecules cannot assemble, thereby abolishing their transport to the cell membrane and the subsequent recognition by antigen-specific T cells. Here we report a case of defective antigen presentation caused by the expression of a beta(2)m with a Cys-to-Trp substitution at position 25 (beta(2)m(C25W)).

Structural and functional characterization of peptide-beta2m fused HLA-A2/MART1(27-35) complexes.

The uses of soluble HLA class I/peptide complexes to monitor antigen reactive T cells are often hampered by their low-yield and high-cost production. As an alternative strategy, the peptide-beta(2)m fused, 2-component (2C) HLA class I/peptide complex has been developed, but its application is limited due to the lack of the comparison of its structural and functional characteristics with those of its conventional 3-component (3C) counterpart. In this study, we have demonstrated that the 2C and 3C HLA-A2/MART1(27-35) complexes have a similar chromatographical profile and comparable stability, but the former has 2.