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https://www.readbyqxmd.com/read/29679856/b7-h6-expression-is-induced-by-lipopolysaccharide-and-facilitates-cancer-invasion-and-metastasis-in-human-gliomas
#1
Fengyuan Che, Xiaoli Xie, Long Wang, Quanping Su, Feiyu Jia, Yufu Ye, Lanlan Zang, Jing Wang, Hongyan Li, Yanchun Quan, Cuiping You, Jiawei Yin, Zhiqiang Wang, Gen Li, Yifeng Du, Lijuan Wang
Although great progress has been made in treatment regimens, gliomas are still incurable and the 5-year survival remains poor. Studies focusing on molecules that regulate tumorigenesis or tumor immunity may provide potential therapeutic strategies for patients with glioma. B7-H6 is selectively expressed in tumor cells and plays vital roles in host immune responses. In this study, we demonstrated that B7-H6 was expressed in glioma cell lines, including CRT, U251, SHG-44, SF-295, TG-905 and U373, and tumor tissues isolated from glioma patients...
April 18, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29669784/pd-l1-b7-h1-inhibits-viral-clearance-by-macrophages-in-hsv-1-infected-corneas
#2
Sohyun Jeon, Alexander M Rowe, Kate L Carroll, Stephen A K Harvey, Robert L Hendricks
Immune privilege helps protect the cornea from damaging inflammation but can also impair pathogen clearance from this mucosal surface. Programmed death-ligand 1 (PD-L1 or B7-H1) contributes to corneal immune privilege by inhibiting the function of a variety of immune cells. We asked whether programmed death-1 (PD-1)/PD-L1 interaction regulates HSV-1 clearance from infected corneas. We show that PD-L1 is constitutively expressed in the corneal epithelium and is upregulated upon HSV-1 corneal infection, with peak expression on CD45+ cells NK cells, dendritic cells, neutrophils, and macrophages and CD45- corneal epithelial cells at 4 d postinfection (dpi)...
April 18, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29659672/adi-peg-20-plus-best-supportive-care-versus-placebo-plus-best-supportive-care-in-patients-with-advanced-hepatocellular-carcinoma
#3
G Abou-Alfa, S Qin, B-Y Ryoo, S-N Lu, C-J Yen, Y-H Feng, H Y Lim, F Izzo, M Colombo, D Sarker, L Bolondi, G Vaccaro, W P Harris, Z Chen, R A Hubner, T Meyer, W Sun, J J Harding, E M Hollywood, J Ma, P J Wan, M Ly, J Bomalaski, A Johnston, C-C Lin, Y Chao, L-T Chen
Background: Arginine depletion is a putative target in hepatocellular carcinoma (HCC). HCC often lacks argininosuccinate synthetase, a citrulline to arginine-repleting enzyme. ADI-PEG 20 is a cloned arginine degrading enzyme - arginine deiminase - conjugated with polyethylene glycol. The goal of this study was to evaluate this agent as a potential novel therapeutic for HCC after first line systemic therapy. Methods and Patients: Patients with histologically proven advanced HCC and Child-Pugh up to B7 with prior systemic therapy, were randomized 2:1 to ADI-PEG 20 18 mg/m2 vs...
April 5, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29625896/co-inhibitory-molecule-b7-superfamily-member-1-expressed-by-tumor-infiltrating-myeloid-cells-induces-dysfunction-of-anti-tumor-cd8-t-cells
#4
Jing Li, Younghee Lee, Yanjian Li, Yu Jiang, Huiping Lu, Wenjuan Zang, Xiaohong Zhao, Liguo Liu, Yang Chen, Haidong Tan, Zhiying Yang, Michael Q Zhang, Tak W Mak, Ling Ni, Chen Dong
The molecular mechanisms whereby CD8+ T cells become "exhausted" in the tumor microenvironment remain unclear. Programmed death ligand-1 (PD-L1) is upregulated on tumor cells and PD-1-PD-L1 blockade has significant efficacy in human tumors; however, most patients do not respond, suggesting additional mechanisms underlying T cell exhaustion. B7 superfamily member 1 (B7S1), also called B7-H4, B7x, or VTCN1, negatively regulates T cell activation. Here we show increased B7S1 expression on myeloid cells from human hepatocellular carcinoma correlated with CD8+ T cell dysfunction...
March 29, 2018: Immunity
https://www.readbyqxmd.com/read/29615658/systemic-igf-1-gene-delivery-by-raav9-improves-spontaneous-autoimmune-peripheral-polyneuropathy-sapp
#5
Tong Gao, Nataliia Bogdanova, Sameera Ghauri, Gang Zhang, Jianxin Lin, Kazim Sheikh
Spontaneous autoimmune peripheral polyneuropathy (SAPP) is a mouse model of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) in non-obese diabetic (NOD) mice null for costimulatory molecule, B7-2 gene (B7-2-/- ). SAPP is a chronic progressive and multifocal inflammatory and demyelinating polyneuropathy of spontaneous onset with secondary axonal degeneration. Insulin-like growth factor 1(IGF-1) is a pleiotropic factor with neuroprotective, regenerative, and anti-inflammatory effects with extensive experience in its preclinical and clinical use...
April 3, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29596993/immune-modulation-by-silencing-cd80-and-cd86-production-in-dendritic-cells-using-small-hairpin-rna-to-reduce-heart-transplant-rejection
#6
Zhiqiang Yang, Yujian Liu, Xiaolei Zhou
RNA interference (RNAi) plays a potential role in organ transplantation. Small hairpin RNA (shRNA) is an artificial RNA molecule with a tight hairpin turn that can be used to silence the expression of a target gene. We constructed shRNA targeting on the cluster of differentiation 80 (CD80, B7-1) and the cluster of differentiation 86 (CD86, B7-2) and transfected it into dendritic cells (DCs). Fluorescence real-time PCR and flow cytometry confirmed the gene-silencing effect. Interleukin-2 (IL-2) mRNA expression level decreased in T cells that were cocultured with pB7-shRNA-transfected DCs...
March 26, 2018: Transplant Immunology
https://www.readbyqxmd.com/read/29593422/overexpression-of-hhla2-a-member-of-the-b7-family-is-associated-with-worse-survival-in-human-colorectal-carcinoma
#7
Ziwen Zhu, Weiguo Dong
Background: Colorectal carcinoma (CRC) is one of the most common malignancies, and immunotherapy has opened a new field of cancer treatment in recent years. Generally, CRC does not benefit from immunotherapy. HHLA2, a member of the B7 family, is a novel immune checkpoint molecule, and the prognostic value of HHLA2 in CRC patients and the association between HHLA2 expression and clinicopathological characteristics remains unknown. Materials and methods: This study included 63 patients diagnosed with CRC, and their resected specimens were obtained and constructed as a tissue microarray...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29561406/the-prognostic-value-of-b7-h4-in-pancreatic-cancer-systematic-review-and-meta-analysis
#8
Xin Chen, Lianyuan Tao, Chunhui Yuan, Dianrong Xiu
BACKGROUND: There were many reports suggesting that different kinds of tumors can express B7-H4; however, the prognostic value in cancer was still unclearly. Therefore, we conducted a meta-analysis to investigate the relationship between overexpression of B7-H4 with the prognostic value in pancreatic cancer patients. MATERIALS AND METHODS: The Pubmed, Embase, Cochrane Library, Ovid, Web of Science, and Chinese research database (including CBM, CNKI, and WAN FANG) were searched for related literature published until October 12, 2017...
March 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29561066/safety-immunogenicity-pharmacokinetics-and-efficacy-of-degradation-of-anti-hla-antibodies-by-ides-imlifidase-in-chronic-kidney-disease-patients
#9
Tomas Lorant, Mats Bengtsson, Torsten Eich, Britt-Marie Eriksson, Lena Winstedt, Sofia Järnum, Yvonne Stenberg, Anna-Karin Robertson, Kristina Mosén, Lars Björck, Lars Bäckman, Erik Larsson, Kathryn Wood, Gunnar Tufveson, Christian Kjellman
Safety, immunogenicity, pharmacokinetics and efficacy of the immunoglobulin G-degrading enzyme of Streptococcus pyogenes (IdeS, Imlifidase) was assessed in a single centre, open label ascending dose study in highly sensitised chronic kidney disease patients. Eight patients with cytotoxic panel-reactive antibodies (median cytotoxic PRA of 64%) at enrolment received 1 or 2 intravenous infusions of IdeS on consecutive days (0.12 mg/kg body weight x2 (n=3); 0.25 mg/kg x1 (n=3) or 0.25 mg/kg x2 (n=2)). IgG degradation was observed in all subjects after IdeS treatment, with <1% plasma IgG remaining within 48 hours and remaining low up to 7 days...
March 21, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/29544515/next-generation-of-immune-checkpoint-therapy-in-cancer-new-developments-and-challenges
#10
REVIEW
Julian A Marin-Acevedo, Bhagirathbhai Dholaria, Aixa E Soyano, Keith L Knutson, Saranya Chumsri, Yanyan Lou
Immune checkpoints consist of inhibitory and stimulatory pathways that maintain self-tolerance and assist with immune response. In cancer, immune checkpoint pathways are often activated to inhibit the nascent anti-tumor immune response. Immune checkpoint therapies act by blocking or stimulating these pathways and enhance the body's immunological activity against tumors. Cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), programmed cell death receptor-1 (PD-1), and programmed cell death ligand-1(PD-L1) are the most widely studied and recognized inhibitory checkpoint pathways...
March 15, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29530936/b7-h3-negatively-modulates-ctl-mediated-cancer-immunity
#11
Kimio Yonesaka, Koji Haratani, Shiki Takamura, Hitomi Sakai, Ryoji Kato, Naoki Takegawa, Takayuki Takahama, Kaoru Tanaka, Hidetoshi Hayashi, Masayuki Takeda, Sigeki Kato, Osamu Maenishi, Kazuko Sakai, Yasutaka Chiba, Takafumi Okabe, Keita Kudo, Yoshikazu Hasegawa, Hiroyasu Kaneda, Michiko Yamato, Kenji Hirotani, Masaaki Miyazawa, Kazuto Nishio, Kazuhiko Nakagawa
Purpose: Anti-programmed-death-1 (PD-1) immunotherapy improves survival in non-small cell lung cancer (NSCLC), but some cases are refractory to treatment, thereby requiring alternative strategies. B7-H3, an immune-checkpoint molecule, is expressed in various malignancies. To our knowledge, this study is the first to evaluate B7-H3 expression in NSCLCs treated with anti-PD-1 therapy and the therapeutic potential of a combination of anti-PD-1 therapy and B7-H3 targeting. Experimental Design: B7-H3 expression was evaluated immunohistochemically in patients with NSCLC ( n = 82), and its relationship with responsiveness to anti-PD-1 therapy and CD8+ tumor-infiltrating lymphocytes (TILs) was analyzed...
March 12, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29526824/immunohistochemical-and-image-analysis-based-study-demonstrate-that-several-immune-checkpoints-are-co-expressed-in-non-small-cell-lung-carcinoma-tumors
#12
Edwin Roger Parra, Pamela Villalobos, Jiexin Zhang, Carmen Behrens, Barbara Mino, Stephen Swisher, Boris Sepesi, Annika Weissferdt, Neda Kalhor, John Victor Heymach, Cesar Moran, Jianjun Zhang, Jack Lee, Jaime Rodriguez-Canales, Don Gibbons, Ignacio Ivan Wistuba
BACKGROUND: The understanding of immune checkpoint molecules' co-expression in non-small cell lung carcinoma (NSCLC) is important to potentially design combinatorial immunotherapy approaches. MATERIAL AND METHODS: We studied 225 formalin-fixed, paraffin-embedded tumor tissues from stage I-III NSCLCs-142 adenocarcinomas (ADCs) and 83 squamous cell carcinomas (SCCs)-placed in tissue microarrays. Nine immune checkpoint markers were evaluated; 4 (PD-L1, B7-H3, B7-H4, and IDO-1) expressed predominantly in malignant cells (MCs) and 5 (ICOS, VISTA, TIM3, LAG3, and OX40) expressed mostly in stromal tumor-associated inflammatory cells (TAICs)...
March 8, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29520435/a-phase-i-trial-of-escalating-doses-of-cixutumumab-imc-a12-and-sorafenib-in-the-treatment-of-advanced-hepatocellular-carcinoma
#13
Anthony B El-Khoueiry, Robert O'Donnell, Thomas J Semrad, Philip Mack, Suzette Blanchard, Nathan Bahary, Yixing Jiang, Yun Yen, John Wright, Helen Chen, Heinz-Josef Lenz, David R Gandara
PURPOSE: The insulin-like growth factor (IGF) pathway is activated in hepatocarcinogenesis. Cixutumumab is a monoclonal antibody against human insulin-like growth factor-1 receptor (IGF-1R). Given the cross-talk between the IGF and VEGF pathways, we performed a phase I study of the combination of cixutumumab and sorafenib in hepatocellular cancer (HCC). METHODS: Eligible patients with no prior systemic therapy for advanced HCC and Child-Pugh A to B7 were treated with sorafenib 400 mg BID and escalating doses of cixutumumab (2, 4, or 6 mg/kg IV weekly) in a 3 + 3 design...
March 8, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29507197/b7-h1-maintains-the-polyclonal-t-cell-response-by-protecting-dendritic-cells-from-cytotoxic-t-lymphocyte-destruction
#14
Ling Chen, Takeshi Azuma, Weiwei Yu, Xu Zheng, Liqun Luo, Lieping Chen
Induced B7-H1 expression in the tumor microenvironment initiates adaptive resistance, which impairs immune functions and leads to tumor escape from immune destruction. Antibody blockade of the B7-H1/PD-1 interaction overcomes adaptive resistance, leading to regression of advanced human cancers and survival benefits in a significant fraction of patients. In addition to cancer cells, B7-H1 is expressed on dendritic cells (DCs), but its role in DC functions is less understood. DCs can present multiple antigens (Ags) to stimulate dominant or subdominant T cell responses...
March 20, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29492674/urinary-cd80-a-biomarker-for-a-favorable-response-to-corticosteroids-in-minimal-change-disease
#15
EDITORIAL
Gabriel Cara-Fuentes, Miguel A Lanaspa, Gabriela E Garcia, Mindy Banks, Eduardo H Garin, Richard J Johnson
Minimal Change Disease (MCD) is the most common type of nephrotic syndrome in children. The etiology has remained unknown, although it is commonly thought to be due to an unknown circulating factor that triggers podocyte dysfunction. To date, several changes in podocytes have been reported in MCD, of which one is the expression of CD80, also known as B7.1, which is a costimulatory molecule that is normally expressed on antigen -presenting cells. Some studies suggest that subjects with steroid-sensitive MCD may express CD80 in their podocytes during relapse and that this expression is associated with high urinary levels of CD80...
March 1, 2018: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/29487385/histone-deacetylase-hdac-inhibitor-acy241-enhances-anti-tumor-activities-of-antigen-specific-central-memory-cytotoxic-t-lymphocytes-against-multiple-myeloma-and-solid-tumors
#16
Jooeun Bae, Teru Hideshima, Yu-Tzu Tai, Yan Song, Paul Richardson, Noopur Raje, Nikhil C Munshi, Kenneth C Anderson
Histone deacetylases (HDAC) are therapeutic targets in multiple cancers. ACY241, an HDAC6 selective inhibitor, has shown anti-multiple myeloma (MM) activity in combination with immunomodulatory drugs and proteasome inhibitors. Here we show ACY241 significantly reduces the frequency of CD138+ MM cells, CD4+ CD25+ FoxP3+ regulatory T cells, and HLA-DRLow/- CD11b+ CD33+ myeloid-derived suppressor cells; and decreases expression of PD1/PD-L1 on CD8+ T cells and of immune checkpoints in bone marrow cells from myeloma patients...
February 22, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29484464/pd-l1-b7-h3-and-pd-1-expression-in-immunocompetent-vs-immunosuppressed-patients-with-cutaneous-squamous-cell-carcinoma
#17
Vinod Varki, Olga B Ioffe, Soren M Bentzen, Jon Heath, Ashley Cellini, Josephine Feliciano, Dan P Zandberg
BACKGROUND: To characterize the expression of co-signaling molecules PD-L1, PD-1, and B7-H3 in cutaneous squamous cell carcinoma (cSCC) by immune status. METHODS: We retrospectively analyzed 66 cases of cSCC treated with surgical resection from 2012 to 2015. Immunostained tumor sections were analyzed for percent of tumor cells expressing PD-L1 (Tum-PD-L1%), B7-H3 (Tum-B7-H3%), density of peri and intratumoral CD8 T cells (CD8 density), proportion of CD8 T cells expressing PD-1 (CD8-PD-1%) and of tumor-infiltrating immune cells (TII) expressing PD-L1 (TII-PD-L1%)...
February 27, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29463898/uncoupling-therapeutic-from-immunotherapy-related-adverse-effects-for-safer-and-effective-anti-ctla-4-antibodies-in-ctla4-humanized-mice
#18
Xuexiang Du, Mingyue Liu, Juanjuan Su, Peng Zhang, Fei Tang, Peiying Ye, Martin Devenport, Xu Wang, Yan Zhang, Yang Liu, Pan Zheng
Anti-CTLA-4 monoclonal antibodies (mAbs) confer a cancer immunotherapeutic effect (CITE) but cause severe immunotherapy-related adverse events (irAE). Targeting CTLA-4 has shown remarkable long-term benefit and thus remains a valuable tool for cancer immunotherapy if the irAE can be brought under control. An animal model, which recapitulates clinical irAE and CITE, would be valuable for developing safer CTLA-4-targeting reagents. Here, we report such a model using mice harboring the humanized Ctla4 gene. In this model, the clinically used drug, Ipilimumab, induced severe irAE especially when combined with an anti-PD-1 antibody; whereas another mAb, L3D10, induced comparable CITE with very mild irAE under the same conditions...
February 20, 2018: Cell Research
https://www.readbyqxmd.com/read/29416712/b7-h3-promoted-proliferation-of-mouse-spermatogonial-stem-cells-via-the-pi3k-signaling-pathway
#19
Xuedong Wei, Kai Li, Guangbo Zhang, Yuhua Huang, Jinxing Lv, Miao Li, Lun Zhao, Caibin Fan, Jinxian Pu, Jianquan Hou, Hexing Yuan
Objective: We found seminal B7-H3 was associated with human sperm concentration. However, the mechanism is unclear. The purpose of this study was to investigate the expression of B7-H3 in mouse testis and determine the effects of B7-H3 on the proliferation of mouse spermatogonial stem cells (SSCs) and the underlying mechanisms. Methods: B7-H3 expression in the testis of mice at different ages (3 weeks, 8 weeks, 4 months and 9 months) was detected by western blot and immunohistochemistry...
January 5, 2018: Oncotarget
https://www.readbyqxmd.com/read/29413459/212pb-labeled-b7-h3-targeting-antibody-for-pancreatic-cancer-therapy-in-mouse-models
#20
Benjamin B Kasten, Abhishek Gangrade, Harrison Kim, Jinda Fan, Soldano Ferrone, Cristina R Ferrone, Kurt R Zinn, Donald J Buchsbaum
INTRODUCTION: We recently validated monoclonal antibody (mAb) 376.96 as an effective carrier for targeted α-particle radioimmunotherapy (RIT) with 212Pb in ovarian cancer mouse models. In this study, we tested the binding of radiolabeled mAb 376.96 to human pancreatic ductal adenocarcinoma (PDAC) cells and localization in xenografts in immune-deficient mice and evaluated 212Pb-labeled 376.96 (212Pb-376.96) for PDAC therapy. METHODS: In vitro Scatchard assays assessed the specific binding of 212Pb-376...
December 24, 2017: Nuclear Medicine and Biology
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