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S Kang, C Zhang, T Ohno, M Azuma
The PD-1/B7-H1 pathway regulates immune responses and maintains homeostasis. Here, we identified a unique expression of B7 homolog 1 (B7-H1) on masticatory mucosae in the oral cavity. B7-H1 was physiologically expressed on the dorsal surface of the tongue, gingiva, and hard palate. Other squamous epithelia and other structures of the epithelia did not express B7-H1 in the steady state. Physiological B7-H1 expression on masticatory mucosae was limited on prickle cells, and its expression on basal keratinocytes (KCs) was strictly regulated...
October 12, 2016: Mucosal Immunology
Kentaro Inamura, Yusuke Yokouchi, Maki Kobayashi, Rie Sakakibara, Hironori Ninomiya, Sophia Subat, Hiroko Nagano, Kimie Nomura, Sakae Okumura, Tomoko Shibutani, Yuichi Ishikawa
OBJECTIVES: Compared with non-smoking counterparts, smoking-associated lung cancers have a higher mutational load, resulting in the creation of more tumor neoantigens and increased immunogenicity. B7-H3 (also known as CD276) belongs to a family of immune modulators that includes PD-1 and PD-L1 (also known as B7-H1 or CD274). Considering the evidence that PD-L1 inhibitors have been shown to be more effective against lung cancer in smokers, we herein examined the prognostic interaction of tumor B7-H3 expression level with smoking history in lung adenocarcinoma patients...
October 1, 2016: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
Luisa Klotz, Ivan Kuzmanov, Stephanie Hucke, Catharina C Gross, Vilmos Posevitz, Angela Dreykluft, Andreas Schulte-Mecklenbeck, Claudia Janoschka, Maren Lindner, Martin Herold, Nicholas Schwab, Isis Ludwig-Portugall, Christian Kurts, Sven G Meuth, Tanja Kuhlmann, Heinz Wiendl
Molecular mechanisms that determine lesion localization or phenotype variation in multiple sclerosis are mostly unidentified. Although transmigration of activated encephalitogenic T cells across the blood-brain barrier (BBB) is a crucial step in the disease pathogenesis of CNS autoimmunity, the consequences on brain endothelial barrier integrity upon interaction with such T cells and subsequent lesion formation and distribution are largely unknown. We made use of a transgenic spontaneous mouse model of CNS autoimmunity characterized by inflammatory demyelinating lesions confined to optic nerves and spinal cord (OSE mice)...
October 11, 2016: Proceedings of the National Academy of Sciences of the United States of America
Man Li, Zhen-Hua Zhou, Xue-Hua Sun, Xin Zhang, Xiao-Jun Zhu, Shu-Gen Jin, Ya-Ting Gao, Yun Jiang, Yue-Qiu Gao
B7-H1 binding to programmed death-1 may deliver a coinhibitory signal to T cells that is involved in the regulation of T-cell activation and tolerance. B7-H1 plays a key role in dysfunction of dendritic cells (DCs) during chronic HBV infection, but the expression mechanism of B7-H1 remains unclear. One hundred and twenty-nine patients with chronic HBV infection were categorized into either the immune tolerance phase (HBV-IT), the immune clearance phase (HBV-IC), or the inactive carrier phase (HBV-IA). Twenty healthy volunteers were enrolled as controls...
September 12, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
Hanqing Chen, Zhengpeng Shi, Bing Gao, Fengqing Fu, Xueguang Zhang
Objective To investigate the expression and biological significance of costimulatory molecule B7-H6, a member of B7 family, in glioma stem like cells (GSLCs). Methods In virtue of the ability of forming neurospheres in vitro , GSLCs were isolated from U87 cells by cell sub-cloning. Real-time quantitative PCR and flow cytometry were performed to detect the expressions of stem cell related markers (c-myc, Sox2, CD133, nestin, and CXCR4), as well as the expressions of B7 family molecules. The different doses of adriamycin, carboplatin, cisplatin, were used to treat GSLCs for testing their chemotherapy-resistance...
September 2016: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
Stefanie Trojandt, Iris Bellinghausen, Angelika B Reske-Kunz, Matthias Bros
Immature dendritic cells (iDCs) and tolerogenic DCs are essential for the induction and maintenance of peripheral tolerance. Tumors produce immuno-modulatory factors which imprint a pro-tolerogenic, maturation-resistant state in DCs. Here we asked for common markers of differentially tolerized human monocyte-derived DC populations. For this, PBMC-derived monocytes were differentiated to DCs in the presence of established immuno-modulators as released by tumors (IL-6, IL-10, TGF-ß, glucocorticoid [GC], prostaglandin E2 [PGE2])...
September 1, 2016: Human Immunology
Chiara Nicolazzo, Cristina Raimondi, MariaLaura Mancini, Salvatore Caponnetto, Angela Gradilone, Orietta Gandini, Maria Mastromartino, Gabriella Del Bene, Alessandra Prete, Flavia Longo, Enrico Cortesi, Paola Gazzaniga
Controversial results on the predictive value of programmed death ligand 1 (PD-L1) status in lung tumor tissue for response to immune checkpoint inhibitors do not allow for any conclusive consideration. Liquid biopsy might allow real-time sampling of patients for PD-L1 through the course of the disease. Twenty-four stage IV NSCLC patients included in the Expanded Access Program with Nivolumab were enrolled. Circulating tumor cells (CTCs) were analyzed by CellSearch with anti-human B7-H1/PD-L1 PE-conjugated antibody...
2016: Scientific Reports
Sabine Groeger, H P Howaldt, H Raifer, S Gattenloehner, T Chakraborty, J Meyle
B7-H1 and B7-DC ligands are members of the B7 family with important regulatory functions in cell-mediated immune response. Both receptors are ligands of the programmed death receptor PD-1. B7-H1 expression has been detected in the majority of human carcinomas in vivo. B7-H1 mediated signals are able to negatively regulate activated T cell functions and survival, and enable tumor cells to overcome host response. The aim of this study was to investigate the expression of B7-H1 and B7-DC proteins in oral squamous cell carcinomas (OSCC) in vivo...
August 8, 2016: Pathology Oncology Research: POR
Mariko Ishibashi, Hideto Tamura, Mika Sunakawa, Asaka Kondo-Onodera, Namiko Okuyama, Yasuko Hamada, Keiichi Moriya, Inhak Choi, Koji Tamada, Koiti Inokuchi
B7 homolog 1 (B7-H1)-expressing myeloma cells not only inhibit myeloma-specific cytotoxic T lymphocytes (CTL), but also confer a proliferative advantage: resistance to antimyeloma chemotherapy. However, it remains unknown whether B7-H1 expressed on myeloma cells induces cellular responses associated with aggressive myeloma behaviors. To address this question, we analyzed the proliferation and drug sensitivity of B7-H1-expressing myeloma cells transfected with B7-H1-specific short-hairpin RNA or treated with programmed cell death (PD)-1-Fc-coupled beads...
September 2, 2016: Cancer Immunology Research
K Chen, H T Huang, W J Hang, L B Pan, H T Ma
B7 homolog 1 (B7-H1) is the most potent immunoinhibitory molecule in the B7 family. In this study, we examined the effects of tumor-associated B7-H1 on T-cell proliferation in lung cancer. The expression of B7-H1 in human adenocarcinoma A549 and mouse Lewis lung carcinoma (LLC) cells were examined by flow cytometry. To assess the in vitro effect of tumor-associated B7-H1 on T-cell proliferation, we isolated T cells from peripheral blood mononuclear cells (PBMCs) of healthy individuals, labeled them with carboxyfluorescein succinimidyl ester, and co-cultured them with A549 cells in the absence or presence of anti-B7-H1 antibody...
June 20, 2016: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
Yohei Masugi, Reiko Nishihara, Juhong Yang, Kosuke Mima, Annacarolina da Silva, Yan Shi, Kentaro Inamura, Yin Cao, Mingyang Song, Jonathan A Nowak, Xiaoyun Liao, Katsuhiko Nosho, Andrew T Chan, Marios Giannakis, Adam J Bass, F Stephen Hodi, Gordon J Freeman, Scott Rodig, Charles S Fuchs, Zhi Rong Qian, Shuji Ogino
OBJECTIVE: Evidence suggests that CD274 (programmed death-ligand 1, B7-H1) immune checkpoint ligand repress antitumour immunity through its interaction with the PDCD1 (programmed cell death 1, PD-1) receptor of T lymphocytes in various tumours. We hypothesised that tumour CD274 expression levels might be inversely associated with T-cell densities in colorectal carcinoma tissue. DESIGN: We evaluated tumour CD274 expression by immunohistochemistry in 823 rectal and colon cancer cases within the Nurses' Health Study and Health Professionals Follow-up Study...
May 5, 2016: Gut
Mei Xu, Bei Zhang, Meng Zhang, Yang Liu, Feng-Ling Yin, Xia Liu, Shi-Chao Zhuo
The aim of the present study was to investigate the expression of B7-H1 and B7-H4 in ovarian neoplasm tissues and to examine their clinical relevance. A total of 112 ovarian biopsies were collected from patients with epithelial ovarian cancer (EOC) and 10 were taken from ovarian benign neoplasms. The samples were processed in paraffin tissue chips, and subjected to immunohistochemical staining and analysis. Associations of B7-H1 and B7-H4 expression with patients' clinical parameters, such as histological typing, cell grading, International Federation of Gynecology and Obstetrics staging, tumor size, and metastatic status, were examined by statistical analysis...
April 2016: Oncology Letters
Weiping Zou, Jedd D Wolchok, Lieping Chen
PD-L1 and PD-1 (PD) pathway blockade is a highly promising therapy and has elicited durable antitumor responses and long-term remissions in a subset of patients with a broad spectrum of cancers. How to improve, widen, and predict the clinical response to anti-PD therapy is a central theme in the field of cancer immunology and immunotherapy. Oncologic, immunologic, genetic, and biological studies focused on the human cancer microenvironment have yielded substantial insight into this issue. Here, we focus on tumor microenvironment and evaluate several potential therapeutic response markers including the PD-L1 and PD-1 expression pattern, genetic mutations within cancer cells and neoantigens, cancer epigenetics and effector T cell landscape, and microbiota...
March 2, 2016: Science Translational Medicine
David A Rhodes, Walter Reith, John Trowsdale
Butyrophilin molecules (commonly contracted to BTN), collectively take their name from the eponymous protein in cow's milk. They are considered to be members of the B7 family of costimulatory receptors, which includes B7.1 (CD80), B7.2 (CD86), and related molecules, such as PD-L1 (B7-H1, CD274), ICOS-L (CD275), and B7-H3 (CD276). These coreceptors modulate T cell responses upon antigen presentation by major histocompatibility complex and cognate αβ T cell receptor engagement. Molecules such as BTN3A1 (CD277), myelin oligodendrocyte glycoprotein, and mouse Skint1 and Btnl2, all members of the butyrophilin family, show greater structural and functional diversity than the canonical B7 receptors...
May 20, 2016: Annual Review of Immunology
Laura Pinton, Samantha Solito, Vera Damuzzo, Samuela Francescato, Assunta Pozzuoli, Antonio Berizzi, Simone Mocellin, Carlo Riccardo Rossi, Vincenzo Bronte, Susanna Mandruzzato
The expansion of myeloid derived suppressor cells (MDSCs), a suppressive population able to hamper the immune response against cancer, correlates with tumor progression and overall survival in several cancer types. We have previously shown that MDSCs can be induced in vitro from precursors present in the bone marrow and observed that these cells are able to actively proliferate in the presence of activated T cells, whose activation level is critical to drive the suppressive activity of MDSCs. Here we investigated at molecular level the mechanisms involved in the interplay between MDSCs and activated T cells...
January 12, 2016: Oncotarget
Hamid Reza Safaei, Ayoob Rostamzadeh, Omid Rahmani, Mohsen Mohammadi, Omar Ghaderi, Hamid Yahaghi, Koroosh Ahmadi
In order to evaluate the correlation of B7-H4 and B7-H1 with renal cell carcinoma (RCC), we analyzed B7-H1 and B7-H4 expressions and their clinical significance by immunohistochemical method. Our result indicated that B7-H4-positive staining was detected in 58.13 % of RCC tissues (25 tissues tumors), and there were 18 tissues of patients without detectable B7-H4. Furthermore, 21 cases (48.83 %) were B7-H1-positive. Positive tumor expressions of B7-H4 and B7-H1 were markedly related to advanced TNM stage (P = 0...
June 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
L V Sakhno, E Ya Shevela, M A Tikhonova, A A Ostanin, E R Chernykh
The phenotypic and functional features of human M2 macrophages, in particular, their immunosuppressive activity, can considerably vary depending on M2 polarizing stimulus. This study was aimed at the investigation of cytokine production and pro-apoptogenic/inhibitory molecule expression in macrophages generated with GM-CSF using either standard conditions (M1) or deficiency of serum/growth factors (M2-LS cells). In contrast to M1, M2-LS cells were characterized by an enhanced content of CD206(+), B7-H1(+), FasL(+) and TRAIL(+) cells along with a decreased production of IFN-γ, IL-5, IL-6, IL-13, TNF-α, IL-17 and MCP-1...
February 2016: Scandinavian Journal of Immunology
I Peters, H Tezval, M W Kramer, M Wolters, V Grünwald, M A Kuczyk, J Serth
The era of cytokines, given to patients with metastatic renal cell carcinoma (mRCC) as part of an unspecific immunomodulatory treatment concept, seems to have ended with the introduction of targeted therapies. However, preliminary data from studies on treatment with checkpoint inhibitors (e. g. anti-PD-1 and anti-PD-L1) may point the way to second-generation immunotherapy. The rationale of such immunomodulatory treatment is to stop or interrupt the tumour from "escaping" the body's immune defence. Thompson et al...
November 2015: Aktuelle Urologie
Qiu-Xia Qu, Qin Huang, Yu Shen, Yi-Bei Zhu, Xue-Guang Zhang
Tumor-associated macrophages (TAMs) have been characterized as a critical population of immunosuppressive cells in a variety of tumor types. PD-L1 (also termed B7-H1) has been described to exert co-inhibitory and immune regulatory functions. Here, in ovarian cancer, PD-L1 is selectively overexpressed on some TAM compared that of benign ovarian disease. When expanding the data in peripheral blood, the proportion of PD-L1(+)CD68(+) cell among CD68(+) cells and the intensity of PD-L1 staining on CD68(+) cell in healthy group were similar to that observed in ovarian cyst group; instead, these two measures were significantly higher in ovarian cancer group, thereafter related to TNM stage...
April 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Ashley Cimino-Mathews, Elizabeth Thompson, Janis M Taube, Xiaobu Ye, Yao Lu, Alan Meeker, Haiying Xu, Rajni Sharma, Kristen Lecksell, Toby C Cornish, Nathan Cuka, Pedram Argani, Leisha A Emens
Programmed death ligand 1 (PD-L1) expression by tumor-infiltrating lymphocytes (TILs) and tumor cells in breast cancer has been reported, but the relationships between PD-L1 expression by TIL, carcinoma cells, and other immunologic features of the breast tumor microenvironment remain unclear. We therefore evaluated the interrelationships between tumor cell surface and TIL PD-L1 expression, lymphocyte subpopulations, and patterns of immune cell infiltration in cohorts of treatment-naive, primary breast cancers (PBCs) (n = 45) and matched PBC and metastatic breast cancers (MBC) (n = 26)...
January 2016: Human Pathology
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