Search

Immunotherapy has become the cornerstone of current malignant tumor treatment. However, the response of different patients to immunotherapy is highly heterogeneous, and not all patients can benefit from it. There is an urgent need to find biomarkers that can effectively predict the efficacy of immunotherapy. C-C chemokine ligand 4 (CCL4) is a cytokine, belonging to the inflammatory CCL subfamily. It is mainly secreted by immune cells and tumor cells and shows low or no expression in normal tissues but abnormally high expression in various malignant tumor tissues. After binding to CCL4 and its receptor C-C chemokine receptor type 5 (CCR5), it can recruit and mediate immune cell migration, destroy the stability of the tumor microenvironment (TME), participate in carcinogenesis and promote the development of tumors. In the tumor immune microenvironment, CCL4 can mediate and recruit the directed migration of key immune cells such as monocytes, macrophages, natural killer (NK) cells, and T cells, which makes it a potentially important element affecting the efficacy of immunotherapy and has specific value. This paper reviews the research progresses of CCL4's effects on immune escape in TME, in order to provide clues and references for basic research and clinical diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Metastasis is the leading cause of death in cancer patients. Eliciting anti-tumor immune responses against lung metastasis is hindered by the immunosuppressive microenvironment. This study explored a biomimetic nanoformulation, comprising a nanovaccine (OP) that delivers tumor antigens and adjuvants spatially and temporally in a virus-like manner, and a pulmonary surfactant-biomimetic liposome with an immunomodulator, JQ1 (PS-JQ1). The findings of this study showed that intratracheal administration of OP+PS-JQ1 activated lung immune cells without concomitant excess inflammation, enhanced tumor antigen cross-presentation, generated a significantly high antigen-specific CD8+ T cell response, and reshaped the immunocellular composition in B16 melanoma tumor-bearing lung. OP+PS-JQ1 nanoformulation exhibited a striking immunotherapeutic efficacy, induced local and systemic tumor suppression, improved survival of mice, initiated immune memory that prevents recurrence of secondary tumors. This stable and nontoxic nanoformulation provides a simple, flexible, and robust strategy for augmenting anti-tumor immunity for metastatic cancer. Egg glue proteins are produced by female insects, which can make the eggs firmly attached to the oviposition sites, not affected by wind and rain. However, genes encoding insect egg glue proteins have not yet been reported, and the molecular mechanism underpinning their adhesion is still unknown. Our study makes a significant contribution to the literature as it identifies the sequence, structure, adhesive property, and mechanism of silkworm egg glue protein. Furthermore, it outlines key insights into the structure-function relationships associated with egg glue proteins. We believe that this paper will be of interest to the readership of your journal as it identifies the first complete sequence of insect egg glue proteins, thereby highlighting their potentials future applications in both the biomedical and technical fields. [Display omitted] [ABSTRACT FROM AUTHOR]

Programmed cell death receptor 1 (PD-1) is a membrance-spanning protein mostly expressed in the T cell, and combines with programmed cell death ligand 1 (PD-L1) in the targeting cell. When binding to the ligand on tumor cells, PD-1 as an immunosuppressive molecule, can inhibit the immune function of T cells, thus tumor immune escape. For example, depletion of peripheral effector T cell and accelerate the transformation of effector T cells into regulator T cells. To solve this problem, PD-1 antibody is used to bind to PD-1 on T cells to inhibit the interaction between PD-1 on the T cells and PD-L1 on the tumor cells so that it can restore the function of T cells to kill tumor cell. PD-1 antibodies, such as Nivolumab and Pembrolizumb, are approved as a first-line treatment for advanced non-small cell lung cell cancer. However, due to the interaction of tumor cells, T cells and cytokines, some patients developed drug resistance which reduces the efficacy of immunotherapy. Hence, how to overcome resistance has become a urgent problem. Cereblon (CRBN), a substrate receptor of the DDB1-cullin-RING E3 ubiquitin ligase complex and the only known molecular receptor of immunoregulatory drugs, has been found to reverse PD-1 antibody resistance by binding to CRBN regulatory agents (CMS), exert T cell immune function by regulating proliferation, activation and metabolism of T cell. In this paper, the mechanism of down-regulation of T cells leading to resistance of PD-1 antibody in lung cancer, the mechanism of CRBN regulating T cells, and research progress of CRBN regulator in the treatment of lung cancer were reviewed. [ABSTRACT FROM AUTHOR]

In the present paper, a HIV - 1 infection of CD 4 + T-cells with the impact of drug treatment model of arbitrary order have been examined with the aid of Legendre wavelet operational matrix method. The technique employed to convert differential equations of arbitrary order into the linear or nonlinear algebraic equations, which are easy to handle by mathematical software. The comparison among the discussed methods with RK4, homotopy perturbation scheme, homotopy analysis approach, Laplace adomian-decomposition technique and Adam-Bashforth predictor-corrector scheme divulge that the present technique is authentic and valid for other engineering problems. It is noticed that the suggested scheme are more efficient and effective. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Computer Science & Technology (JCS&T) is the property of Journal of Computer Science & Technology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

hronic obstructive pulmonary disease (COPD) and lung cancer are global high incidence and high mortality diseases, which seriously increase the socio-economic burden. Smoke exposure, genetic susceptibility and chronic inflammation are common susceptible factors. At present, abnormal inflammatory immune response plays an important role in the occurrence and development of the two diseases. In the process of immune response, tumor microenvironment (TME) is gradually produced, which is beneficial to angiogenesis and immunosuppression, and finally leads to immune escape of tumor cells, leading to tumor formation. In this paper, the present situation of COPD complicated with lung cancer and the relationship between abnormal immune response, especially Treg/Th17, and its occurrence and development are briefly reviewed. [ABSTRACT FROM AUTHOR]

With the in-depth study of tumor immunity, immunotherapy represented by immune checkpoint inhibitors has made a great breakthrough in solid tumors. Small cell lung cancer (SCLC) accounts for about 15%-20% of all lung cancers, with high malignancy, early metastasis and lack of effective treatment strategy. The appearance of immune checkpoint inhibitors brings new hope for SCLC. Several clinical trials have demonstrated the persistent efficacy and clinical activity of the programmed death receptor/ligand 1 (PD-1/L1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4) in the treatment of SCLC. However, its efficacy and safety are not very accurate, and the markers that can effectively predict the efficacy of immunotherapy have not been concluded. In this paper, for further changing the treatment strategy of SCLC clinical practice and providing theoretical basis of research, we reviewed the progress of immune checkpoint inhibitors, related markers in the treatment of SCLC by exploring the value, problems and challenges of immunotherapy in SCLC. [ABSTRACT FROM AUTHOR]

New therapies for systemic lupus erythematosus are rare. This is because of the complexity of the disease and its varied presentations. There are many variables and a variety of measurement scales that must be satisfied before a new agent is approved for use in humans. Attempts are ongoing to develop biological treatments for the disease using three approaches: B cell modulation, T cell regulation and cytokine inhibition. This paper reviews the current state of these three critical areas. [ABSTRACT FROM AUTHOR]

This paper presents the METINUS Plus (METhod of Immunohistochemical NUclei Segmentation Plus) method that has been developed for localization and quantification of the regulatory T cells’ nuclei. The proposed methodology performs color separation followed by the extraction and validation of objects. Objects categorized as clusters, based on the area and shape, are divided with locally applied watershed supported by color deconvolution. Objects are validated based on RGB, Lab color space, and color deconvolution data. The chosen validation criteria allow quantification and differentiation between the subpopulations of regulatory T cells and breast cancer cells, which express FOXP3. The evaluation is based on the quantity and quality of nuclei segmentation in comparison with the results of the manual counting, done by four pathologists on a set of 20 images. The results were analyzed in comparison with human evaluation using Kendall's tau-b correlation coefficient and the Wilcoxon signed-rank test. The main achievement of this study is a possibility to find criteria that allow differentiation between two types of immunopositive cells’ nuclei: regulatory T cells with homogeneous stained nuclei and all cells with FOXP3 expression; in both tumor and axillary node biopsies. A major advantage of computer image processing is the reproducibility of achieved results, thus minimizing human intervention, and providing traceable clinical information. [ABSTRACT FROM AUTHOR]

A defining characteristic of persistent viral infections is the loss and functional inactivation of antiviral effector T cells, which prevents viral clearance. Interleukin-10 (IL-10) suppresses cellular immune responses by modulating the function oft cells and antigen-presenting cells. In this paper, we report that IL-10 production is drastically increased in mice persistently infected with lymphocytic choriomeningitis virus. In vivo blockade of the IL-10 receptor (IL-10R) with a neutralizing antibody resulted in rapid resolution of the persistent infection. IL-10 secretion was diminished and interferon γ production by antiviral CD8+ T cells was enhanced. In persistently infected mice, CD8α+ dendritic cell (DC) numbers declined early after infection, whereas CD8α- DC numbers were not affected. CD8α- DCs supported IL-10 production and subsequent dampening of antiviral T cell responses Therapeutic IL-10R blockade broke the cycle of IL-10-mediated immune suppression, preventing IL-10 priming by CD8α- DCs and enhancing antiviral responses and thereby resolving infection without causing immunopathology. [ABSTRACT FROM AUTHOR]

T cells recognize protein antigens as short peptides processed and displayed by antigen-presenting cells. However, the mechanism of peptide selection is incompletely understood, and, consequently, the differences in the immunogenicity of protein antigens remain largely unpredictable and difficult to manipulate. In this paper we show that the susceptibility of protein antigens to lysosomal proteolysis plays an important role in determining immunogenicity in vivo. We compared the immunogenicity of proteins with the same sequence (same T cell epitopes) and structure (same B cell epitopes) but with different susceptibilities to lysosomal proteolysis. After immunizing mice with each of the proteins adsorbed onto aluminum hydroxide as adjuvant, we measured serum IgG responses as a physiological measure of the antigen's ability to be presented on major histocompatibility complex class II molecules and to prime CD4+ T cells in vivo. For two unrelated model antigens (RNase and horseradish peroxidase), we found that only the less digestible forms were immunogenie, inducing far more efficient T cell priming and antibody responses. These findings suggest that stability to lysosomal proteolysis may be an important factor in determining immunogenicity, with potential implications for vaccine design. [ABSTRACT FROM AUTHOR]

CD4+ T cells are classically thought to orchestrate adaptive immune responses. But recent studies demonstrate that they can also kill infected cells directly. A new paper shows that highly efficient processing of Epstein Barr virus (EBV) glycoproteins for presentation on MHC class II makes virus-transformed B cells susceptible to lysis by CD4+ T cells. Thus, antiviral vaccines should aim to stimulate both helper and cytolytic CO4+ T cells. [ABSTRACT FROM AUTHOR]

Copyright of Revista da Faculdade de Odontologia is the property of UFRGS-Faculdade de Odontologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Quantitative and qualitative aspects of commensal bacteria determine the active and quiescent status of host immunity. In a recent Science paper, identify Clostridium clusters IV and XIVa as indigenous commensal bacteria that induce regulatory T cells for the creation and maintenance of immunological homeostasis. [Copyright &y& Elsevier]