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High expression of CD28 enhanced the anti-cancer effect of siRNA-PD-1 through prompting the immune response of melanoma-bearing mice
Int Immunopharmacol. 2022 Jan 27;105:108572. doi: 10.1016/j.intimp.2022.108572. Online ahead of print.ABSTRACTImmune checkpoint blockade is considered to be an effective method of tumor immunotherapy. As one of the main immune checkpoints, blocking PD-1/PD-L1 pathway has been proved to be effective in the treatment of many cancers via activating T cells; however, many patients still do not respond to the blocking PD-1/PD-L1 treatment with satisfying results. Related research demonstrated that the activation of T cells required a co-stimulatory signal generated by the interaction between CD28 and CD80/CD86, whereas in many ...
Source: International Immunopharmacology - January 30, 2022 Category: Allergy & Immunology Authors: Huijie Jia Jing Guo Zhiang Liu Pengfei Chen Yang Li Ruipeng Li Yunfan Yang Xinyi Li Pengkun Wei Jiateng Zhong Feng Ren Mingyong Wang Jianzhuang Ren Zhiwei Feng Tiesuo Zhao Source Type: research

Antitumor effects and mechanisms of CpG ODN combined with attenuated Salmonella-delivered siRNAs against PD-1.
Abstract Numerous studies have focused on the treatment of melanoma, but the current therapies for melanoma have limited therapeutic effects. To find a more effective therapy for melanoma, we combined artificially designed CpG ODN (cytosine-phosphate-guanine oligodeoxynucleotides) and siRNAs (small-interfering ribonucleic acids) targeting PD-1 (programmed cell death protein 1), which were delivered by attenuated Salmonella to treat melanoma in mice, and explored the underlying antitumor mechanisms. We found that mice receiving the combination therapy had the smallest tumor size and the longest survival time. The p...
Source: International Immunopharmacology - December 9, 2020 Category: Allergy & Immunology Authors: Jia X, Guo J, Guo S, Zhao T, Liu X, Cheng C, Wang L, Zhang B, Meng C, Jia H, Luo E Tags: Int Immunopharmacol Source Type: research

LGP2 plays a critical role in MDA5-mediated antiviral activity against duck enteritis virus
In this study, we used overexpression and knockdown methods to determine if MDA5 affected DEV infection in ducks. We confirmed that DEV infection was significantly suppressed in MDA5-overexpressing DEF cells, while knockdown of MDA5 by siRNA markedly enhanced DEV growth. We demonstrated that overexpression of duck MDA5 significantly upregulated expression of interferon (IFN)-stimulated genes, including myxovirus resistance protein (Mx), IFN-induced oligodenylate synthetase-like (OASL), IFN-induced transmembrane protein 1 (IFITM1) and IFN-β. In addition, the transcriptional level of MDA5 was upregulated both in vivo and ...
Source: Molecular Immunology - October 31, 2019 Category: Allergy & Immunology Source Type: research

Human CAR NK Cells: A New Non-viral Method Allowing High Efficient Transfection and Strong Tumor Cell Killing
In conclusion, the method of NK cell transfection described in our present study is highly efficient, does not require expensive dedicated structures necessary for viral transduction and avoids possible risks associated with the use of viral vectors. Importantly, it may be applied to NK cells or NK-92 cell line, greatly improving their anti-tumor activity and providing a new NK cell-based platform for new protocols of adoptive immuno-therapy of cancer. Ethics Statement The Ethical Committee of IRCCS Bambino Gesù Pediatric Hospital approved the study (825/2014). Author Contributions TI designed and performed res...
Source: Frontiers in Immunology - April 29, 2019 Category: Allergy & Immunology Source Type: research

NOD2 and TLR2 Signal via TBK1 and PI31 to Direct Cross-Presentation and CD8 T Cell Responses
The objective of this study was to explore the role of NOD2 and TLR2 in cross-presentation in human dendritic cells undertaking an unbiased screen. We have used a quantitative phosphoproteomic analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS) followed by a computational analysis to identify the proteins as differentially abundant in response to NOD2 and TLR2 sensing. Validation of the phosphoproteomic analysis was performed by the detection of proteins in phosphoenriched lysates and detected by western blot. Techniques for the modulation of gene expression (shRNA and siRNA) were used to confirm the resu...
Source: Frontiers in Immunology - April 29, 2019 Category: Allergy & Immunology Source Type: research

Myeloid Derived Suppressor Cells Interactions With Natural Killer Cells and Pro-angiogenic Activities: Roles in Tumor Progression
Conclusions MDSC are major players in the immunosuppressive scenario in cancer, thanks to their phenotype heterogeneity and critical interaction with several innate immune cells, thus representing a crucial target in oncology. Here we reviewed the interactions of MDSCs with NK cells. The contribution of key cytokines, chemokines and mediators active in this process have been discussed. We also described the contribution of MDSC on angiogenesis directly or indirectly through interactions with NK and immunosuppressive activities. A parallel of the cancer associated to the decidual counterpart of these cells is discussed, a...
Source: Frontiers in Immunology - April 17, 2019 Category: Allergy & Immunology Source Type: research

SOCS and Herpesviruses, With Emphasis on Cytomegalovirus Retinitis
Christine I. Alston1,2 and Richard D. Dix1,2* 1Department of Biology, Viral Immunology Center, Georgia State University, Atlanta, GA, United States 2Department of Ophthalmology, Emory University School of Medicine, Atlanta, GA, United States Suppressor of cytokine signaling (SOCS) proteins provide selective negative feedback to prevent pathogeneses caused by overstimulation of the immune system. Of the eight known SOCS proteins, SOCS1 and SOCS3 are the best studied, and systemic deletion of either gene causes early lethality in mice. Many viruses, including herpesviruses such as herpes simplex virus and cytomega...
Source: Frontiers in Immunology - April 10, 2019 Category: Allergy & Immunology Source Type: research

Complement C5b-9 and Cancer: Mechanisms of Cell Damage, Cancer Counteractions, and Approaches for Intervention
In conclusion, osmotic burst of inflated complement-damaged cells may occur, but these bursts are most likely a consequence of metabolic collapse of the cell rather than the cause of cell death. The Complement Cell Death Mediator: A Concerted Action of Toxic Moieties Membrane pores caused by complement were first visualized by electron microscopy on red blood cell membranes as large ring structures (22). Similar lesions were viewed on E. coli cell walls (23). Over the years, ample information on the fine ultrastructure of the MAC that can activate cell death has been gathered (24) and has been recently further examined (...
Source: Frontiers in Immunology - April 9, 2019 Category: Allergy & Immunology Source Type: research

Novel Application of Radotinib for the Treatment of Solid Tumors via Natural Killer Cell Activation.
This study provides the first evidence that radotinib could be used as an effective and strong therapeutic to treat solid tumors via upregulation of NK cell cytotoxicity, suggesting that radotinib has indirect killing mechanisms via upregulation of antitumor innate immune responses as well as direct killing activities for CML cells. PMID: 30687767 [PubMed - in process]
Source: Journal of Immunology Research - January 29, 2019 Category: Allergy & Immunology Tags: J Immunol Res Source Type: research

CCR5 Blockade Suppresses Melanoma Development Through Inhibition of IL-6-Stat3 Pathway via Upregulation of SOCS3
Abstract In order to understand how tumor cells can escape immune surveillance mechanisms and thus develop antitumor therapies, it is critically important to investigate the mechanisms by which the immune system interacts with the tumor microenvironment. In our current study, we found that chemokine receptor 5 (CCR5) neutralization resulted in reduced melanoma tumor size, decreased percentage of CD11b+Gr-1+ myeloid-derived suppressor cells (MDSCs), and increased proportion of cluster of differentiation (CD)3+ T cells in tumor tissues. Suppressive activity of MDSCs on CD4+ T cells and CD8+ T cell proliferation is s...
Source: Inflammation - June 5, 2015 Category: Allergy & Immunology Source Type: research

TLR3 and MDA5 signalling, although not expression, is impaired in asthmatic epithelial cells in response to rhinovirus infection.
Conclusion and Clinical RelevanceImpaired antiviral responses in asthmatic pBECs are not due to deficient expression of PRRs; MDA5 and TLR3, but an inability to later activate types I and III interferon immune responses to RV infection, potentially increasing susceptibility to the effects of RV infection.
Source: Clinical and Experimental Allergy - December 20, 2013 Category: Allergy & Immunology Authors: K. S. Parsons, A. C. Hsu, P. A. B. Wark Tags: Original Article Source Type: research

TLR3 and MDA5 signalling though not expression, is impaired in asthmatic epithelial cells in response to rhinovirus infection
Conclusion & Clinical RelevanceImpaired antiviral responses in asthmatic pBECs are not due to deficient expression of PRRs; MDA5 and TLR3, but an inability to later activate type I and III interferon immune responses to RV infection, potentially increasing susceptibility to the effects of RV infection.This article is protected by copyright. All rights reserved.
Source: Clinical and Experimental Allergy - October 17, 2013 Category: Allergy & Immunology Authors: Kristy S Parsons, Alan C Hsu, Peter AB Wark Tags: Original Article‐Experimental Models of Allergic Disease Source Type: research