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https://www.readbyqxmd.com/read/29238207/advances-in-t-cell-checkpoint-immunotherapy-for-head-and-neck-squamous-cell-carcinoma
#1
REVIEW
Xinmeng Qi, Bo Jia, Xue Zhao, Dan Yu
Head and neck squamous cell carcinoma (HNSCC) has been found to be a complex group of malignancies characterized by their profound immunosuppression and high aggressiveness. In most cases of advanced HNSCC, treatment fails to obtain total cancer cure. Efforts are needed to develop new therapeutic approaches to improve HNSCC outcomes. In this light, T-cells "immune checkpoint" has attracted much attention in cancer immunotherapy. It has been broadly accepted that inhibitory T-cell immune checkpoints contribute to tumor immune escape through negative immune regulatory signals (cytotoxic T-lymphocyte-associated antigen 4 [CTLA-4], programmed cell death 1 [PD-1], B7-H3, and B7-H4, etc)...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29217739/y90-radioembolization-for-locally-advanced-hepatocellular-carcinoma-with-portal-vein-thrombosis-long-term-outcomes-in-a-185-patient-cohort
#2
Nadine Abouchaleh, Ahmed Gabr, Rehan Ali, Ali Al Asadi, Ronald A Mora, Joseph Ralph Kallini, Karen Marshall, Laura Kulik, Samdeep Mouli, Daniela P Ladner, Michael Abecassis, Juan C Caicedo, Ahsun Riaz, Robert J Lewandoski, Riad Salem
Purpose: To report survival outcomes for advanced stage hepatocellular carcinoma (HCC) with portal vein thrombosis (PVT) treated with radioembolization (Y90). Methods: With IRB approval we searched our prospectively acquired database for patients treated with Y90 between 2003 and 2017. Inclusion criteria were patients who had advanced stage HCC with tumor PVT. In order to minimize confounding effect, patients with metastases were excluded. Clinical and laboratory data were collected at baseline and 1 month post-Y90...
December 7, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29209565/tumor-targeted-costimulation-with-antibody-fusion-proteins-improves-bispecific-antibody-mediated-immune-response-in-presence-of-immunosuppressive-factors
#3
Sabrina Sapski, Nadine Beha, Roland Kontermann, Dafne Müller
Therapeutic strategies aiming for the induction of an effective immune response at the tumor site can be severely hampered by the encounter of an immunosuppressive microenvironment. We investigated here the potential of concerted costimulation by tumor-directed antibody-fusion proteins with B7.1, 4-1BBL and OX40L to enforce bispecific antibody-induced T cell stimulation in presence of recognized immunosuppressive factors including IL-10, TGF-β, indoleamine 2,3-dioxygenase (IDO), PD-L1 and regulatory T cells...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29207326/in-silico-prediction-of-potential-vaccine-candidates-on-capsid-protein-of-human-bocavirus-1
#4
Narayanan Kalyanaraman
Human bocavirus 1 (HBoV1) is a newly identified parvovirus that causes serious respiratory infection among children across the globe. Aim of the present study was to predict immunogenic residues located on the VP2 protein of HBoV1 towards development of epitope based vaccines. Several computational tools were employed to predict epitopes (bothT and B cell restricted) with stringent regulation for the improvement of confidence. After meticulous analysis, the peptide "TTPWTYFNFNQY" was identified as potential candidate for development of preventive vaccine...
December 2, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29190985/prognostic-value-of-b7-h3-expression-in-patients-with-solid-tumors-a-meta-analysis
#5
Xianyun Zhang, Chuntao Fang, Guangbo Zhang, Fujin Jiang, Lei Wang, Jianquan Hou
Increasing evidence suggests B7-H3 is aberrantly expressed in various cancers, though its prognostic significance in solid tumors remains controversial. We therefore performed a meta-analysis to clarify the prognostic value of B7-H3 expression in human solid tumors. The PubMed and Embase databases were searched, and 28 studies involving 4623 patients were ultimately included in the analysis. Hazard ratios (HRs) with 95% confidence intervals (CIs) were utilized as effect estimates to evaluate the association between B7-H3 expression and overall survival (OS), progression-free survival (PFS) and recurrence-free survival (RFS)...
November 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29180896/checkpoint-blockade-in-solid-tumors-and-b-cell-malignancies-with-special-consideration-of-the-role-of-cd200
#6
REVIEW
Reginald M Gorczynski, Fang Zhu
In the ontogeny of a normal immune response, a series of checkpoints must be overcome to ensure that unwanted and/or harmful self-directed activation responses are avoided. Many of the molecules now known to be active in this overseeing of the evolving immune activation cascade, contributing inhibitory signals to dampen an overexuberant response, belong to the immunoglobulin supergene family. These include members of the CD28/CTLA-4:B7.1/B7.2 receptor/ligand family, PD-1 and PDL-1, CD200 and CD200R, and the more recently described V-domain immunoglobulin suppressor of T-cell activation and its ligand (VSIG-3/IGSF11)...
2017: Cancer Management and Research
https://www.readbyqxmd.com/read/29170671/b7-h1-influences-the-accumulation-of-virus-specific-tissue-resident-memory-t-cells-in-the-central-nervous-system
#7
Kevin D Pavelko, Michael P Bell, Susan M Harrington, Haidong Dong
Therapies that target the PD-1/B7-H1 axis have revolutionized cancer treatment, yet precise knowledge of how this pathway provides benefit continues to evolve. Here, we report a novel role for the immune checkpoint ligand B7-H1 in the accumulation of tissue-resident memory CD8(+) T-cells (TRM). After intracranial infection, Theiler's murine encephalomyelitis virus (TMEV) generates TRM that are maintained in the central nervous system (CNS) tissues of B7-H1(WT) animals. Although no differences in acute T-cell responses between B7-H1(WT) and B7-H1(KO) are observed, at long-term periods post-infection the maintenance of CD8(+) TRM is diminished in B7-H1(KO) animals...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29163808/cd4-t-cell-specific-b7-h1-selectively-inhibits-proliferation-of-na%C3%A3-ve-t-cells-and-th17-differentiation-in-experimental-autoimmune-encephalomyelitis
#8
Sheng-Jia Shi, Mei-Ling Ding, Li-Juan Wang, Jie-Heng Wu, Dong-Hui Han, Guo-Xu Zheng, Zhang-Yan Guo, Wen-Jin Xi, Wei-Jun Qin, An-Gang Yang, Wei-Hong Wen
It is widely acknowledged that interleukin 17-producing T helper (Th17) cells are critically participant in the pathogenesis of multiple sclerosis. In the current study, we identified that the expression of CD4(+)T cells specific co-inhibitory molecule B7-homologue 1(B7-H1) in spleenocytes and mononuclear cells isolated from brains and spinal cord were positive correlated with Th1 and Th17 cells generation and disease severity in experimental autoimmune encephalomyelitis (EAE). Furthermore, B7-H1 transgenic mice developed milder EAE symptoms and fewer Th17 cells than B7-H1 wild type mice...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29145450/enhanced-expression-of-cell-surface-b-cell-receptor-associated-protein-31-contributes-to-poor-survival-of-non-small-cell-lung-carcinoma-cells
#9
Se-Ri Seo, Hyun Min Lee, Hong Seo Choi, Won-Tae Kim, Eun-Wie Cho, Chun Jeih Ryu
B-cell receptor-associated protein 31 (BAP31) is an endoplasmic reticulum (ER) membrane protein which plays a role as a molecular chaperone for the newly synthesized transmembrane proteins. BAP31 is also an important apoptosis regulator for extrinsic apoptosis induction in the ER membrane. Recent studies have shown that BAP31 is also expressed on the surface of embryonic stem cells. However, the function of cell surface BAP31 (csBAP31) still remains unclarified. In an attempt to search for surface markers on tumorspheres, here, we generated monoclonal antibodies (MAbs) against the sphere cells from the non-small cell lung carcinoma cell (NSCLC) line A549...
2017: PloS One
https://www.readbyqxmd.com/read/29137299/tumor-expressed-immune-checkpoint-b7x-promotes-cancer-progression-and-antigen-specific-cd8-t-cell-exhaustion-and-suppressive-innate-immune-cells
#10
Kim C Ohaegbulam, Weifeng Liu, Hyungjun Jeon, Steven C Almo, Xingxing Zang
B7x (B7-H4 or B7S1) is a coinhibitory member of the B7 immune checkpoint ligand family that regulates immune function following ligation with its unknown cognate receptors. B7x has limited expression on normal tissues, but is up-regulated on solid human tumors to inhibit anti-tumor immunity and associates with poor clinical prognosis. We assessed the contribution of cytokine stimuli to induce surface B7x expression on cancer cells and the role of tumor-expressed B7x in a murine pulmonary metastasis model, and finally evaluated the potential interaction between B7x and Neuropilin-1, a suggested potential cognate receptor...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29104629/association-between-b7-h1-and-cervical-cancer-b7-h1-impairs-the-immune-response-in-human-cervical-cancer-cells
#11
Jianying Tao, Jianrong Dai, Shunyu Hou
The aim of the present study was to determine the preliminary mechanism of action of B7 homolog 1 (B7-H1) and investigate the association between B7-H1 and cervical cancer. The expression of B7 family proteins was measured in cervical cancer cells. Cervical cancer cells were co-cultured with T lymphocytes. An ELISA assay was subsequently conducted to analyze cytokine concentrations in the supernatants of the cultured T cells in cervical cancer cells and B7-H1 downregulated cells. Levels of interleukin (IL)-1β, IL-6 and tumor necrosis factor-α mRNA in mice injected with cervical cancer cells or B7-H1 downregulated cells were measured by reverse transcription-quantitative polymerase chain reaction...
November 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29090321/cross-talk-between-tnf-%C3%AE-and-ifn-%C3%AE-signaling-in-induction-of-b7-h1-expression-in-hepatocellular-carcinoma-cells
#12
Na Li, Jianing Wang, Na Zhang, Mengwei Zhuang, Zhaoyun Zong, Jiahuan Zou, Guosheng Li, Xiaoyan Wang, Huaiyu Zhou, Lining Zhang, Yongyu Shi
Clinical benefit from immunotherapy of B7-H1/PD-1 checkpoint blockade indicates that it is important to understand the regulatory mechanism of B7-H1 expression in cancer cells. As an adaptive response to the endogenous antitumor immunity, B7-H1 expression is up-regulated in HCC cells. B7-H1 expression is induced mainly by IFN-γ released from tumor-infiltrating T cells in HCC. In addition, HCC is a prototype of inflammation-related cancer and TNF-α is a critical component of inflammatory microenvironment of HCC...
October 31, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29069644/interactive-effects-of-snps-located-within-cd28-b7pathway-and-environment-on-susceptibility-to-recurrent-spontaneous-abortion
#13
Guiling Wang, Jing Sun
AIMS: This study was aimed to explore the interaction between environment and CD28/B7 pathway to provide the potential epidemiology for prevention and treatment of recurrent spontaneous abortion (RSA). METHODS: The retrospective study included 630 RSA cases and 1320 healthy women during their middle and late prenatal care. Their living environment was investigated, and the influence of environmental factors on pregnancy abortion was analyzed. The genomic DNAs were extracted from the study subjects, and the polymorphisms of CD28 and B7 were analyzed...
October 25, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29056539/tumor-cell-associated-immune-checkpoint-molecules-drivers-of-malignancy-and-stemness
#14
REVIEW
Fabrizio Marcucci, Cristiano Rumio, Angelo Corti
Inhibitory or stimulatory immune checkpoint molecules are expressed on a sizeable fraction of tumor cells in different tumor types. It was thought that the main function of tumor cell-associated immune checkpoint molecules would be the modulation (down- or upregulation) of antitumor immune responses. In recent years, however, it has become clear that the expression of immune checkpoint molecules on tumor cells has important consequences on the biology of the tumor cells themselves. In particular, a causal relationship between the expression of these molecules and the acquisition of malignant traits has been demonstrated...
October 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29039509/evaluation-of-a-novel-dry-eye-model-induced-by-oral-administration-of-finasteride
#15
Kai Li, Chuanwei Zhang, Zichao Yang, Yuliang Wang, Haipeng Si
Dry eye is a common eye disease, and suitable animal models are indispensable for investigating the pathogenesis and developing treatments for dry eye. The present study was conducted to develop an androgen deficiency dry eye model induced by finasteride, and to evaluate ocular surface status and inflammatory cytokine gene expression in the lacrimal gland using a cytokine antibody array system. The results revealed that the antiandrogenic drug finasteride induced significant tear deficiency, and the histopathology results revealed significant inflammatory cell infiltration in the lacrimal gland...
December 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29033832/cyclotides-isolated-from-an-ipecac-root-extract-antagonize-the-corticotropin-releasing-factor-type-1-receptor
#16
Mohsen Fahradpour, Peter Keov, Carlotta Tognola, Estela Perez-Santamarina, Peter J McCormick, Alireza Ghassempour, Christian W Gruber
Cyclotides are plant derived, cystine-knot stabilized peptides characterized by their natural abundance, sequence variability and structural plasticity. They are abundantly expressed in Rubiaceae, Psychotrieae in particular. Previously the cyclotide kalata B7 was identified to modulate the human oxytocin and vasopressin G protein-coupled receptors (GPCRs), providing molecular validation of the plants' uterotonic properties and further establishing cyclotides as valuable source for GPCR ligand design. In this study we screened a cyclotide extract derived from the root powder of the South American medicinal plant ipecac (Carapichea ipecacuanha) for its GPCR modulating activity of the corticotropin-releasing factor type 1 receptor (CRF1R)...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28994323/atezolizumab-in-invasive-and-metastatic-urothelial-carcinoma
#17
Michael Crist, Arjun Balar
Until recently, there has been little advancement in the management of invasive and metastatic urothelial cancer in over 30 years, and outcomes with cisplatin-based chemotherapy remain unchanged. Inhibitors targeting PD-1 signaling on cytotoxic T-cells have revolutionized bladder cancer therapy leading to durable responses. Atezolizumab is an engineered humanized anti-PD-L1 monoclonal antibody that inhibits PD-L1 binding to PD-1 and B7.1, enhancing immune-mediated tumor killing and is currently approved as second-line treatment after failure of platinum-based chemotherapy as well as first-line in cisplatin-ineligible patients...
October 10, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28987965/emerging-targets-in-cancer-immunotherapy
#18
REVIEW
Samantha Burugu, Amanda R Dancsok, Torsten O Nielsen
The first generation of immune checkpoint inhibitors (anti-CTLA-4 and anti-PD-1/PD-L1) targeted natural immune homeostasis pathways, co-opted by cancers, to drive anti-tumor immune responses. These agents led to unprecedented results in patients with previously incurable metastatic disease and may become first-line therapies for some advanced cancers. However, these agents are efficacious in only a minority of patients. Newer strategies are becoming available that target additional immunomodulatory mechanisms to activate patients' own anti-tumor immune responses...
October 5, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28985469/programmed-cell-death-protein-ligand-1-silencing-with-polyethylenimine-dermatan-sulfate-complex-for-dual-inhibition-of-melanoma-growth
#19
Gijung Kwak, Dongkyu Kim, Gi-Hoon Nam, Sun Young Wang, In-San Kim, Sun Hwa Kim, Ick-Chan Kwon, Yoon Yeo
Programmed cell death protein-1 (PD-1) is a prominent immune checkpoint receptor interacting with its ligand, programmed cell death protein ligand-1 (PD-L1, B7-H1). The PD-1/PD-L1 interaction induces functional exhaustion of tumor-reactive cytotoxic T cells and, thus, interferes with antitumor T-cell immunity. In addition, PD-1/PD-L1 interaction promotes tumorigenesis via the mTOR signaling pathway in a group of cancers including melanoma. Based on the dual functions of PD-1/PD-L1 interactions in tumor progression, we hypothesize that siRNA targeting PD-L1 (siPD-L1) will suppress melanoma growth, acting on both immune checkpoint and intrinsic tumorigenesis pathways...
October 24, 2017: ACS Nano
https://www.readbyqxmd.com/read/28978159/b7-h4-as-an-independent-prognostic-indicator-of-cancer-patients-a-meta-analysis
#20
Zibo Meng, Feiyang Wang, Yushun Zhang, Shoukang Li, Heshui Wu
The expression of B7-H4 was observed in a variety of tumors, however the prognostic value in cancer was still controversial. Therefore, we conducted this meta-analysis to explore the potential role of B7-H4 in cancer prognostic prediction. Twenty-seven studies including 3771 patients were brought into the analysis according to the inclusion and exclusion criteria. The pooled results demonstrated that elevated B7-H4 predicted a poor OS (HR = 1.93, 95% CI 1.71-2.18, P < 0.001) and DFS (HR = 1.84, 95% CI 1...
September 15, 2017: Oncotarget
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