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Program death ligand 1/2

Chuanxi Zheng, Wei You, Peng Wan, Xiaochun Jiang, Jinquan Chen, Yuchen Zheng, Wei Li, Jifeng Tan, Shiquan Zhang
Programmed cell death-ligands 1 (PD-L1) is a key immune checkpoint protein and a promising therapeutic target for malignancy tumor immunotherapy. The prognostic value of PD-L1 in patients with bone and soft tissue sarcoma remains controversial. Therefore, this meta-analysis is conducted to evaluate the associations of PD-L1 expression with overall survival (OS), progression-free survival (PFS), and clinicopathological characteristics of sarcomaA comprehensive literature search of PubMed, Web of Science, Embase, and Cochrane Library was conducted for relevant studies...
June 2018: Medicine (Baltimore)
Ellen J Beswick, Carl Grim, Abinav Singh, Jose E Aguirre, Marissa Tafoya, Suimin Qiu, Gerhard Rogler, Rohini McKee, Von Samedi, Thomas Y Ma, Victor E Reyes, Don W Powell, Irina V Pinchuk
Background and Aims: The role of programmed cell death protein 1 (PD-1) and its ligands in the dysregulation of T helper immune responses observed in the inflammatory bowel disease (IBD) is unclear. Recently, a novel concept emerged that CD90+ colonic (myo)fibroblasts (CMFs), also known as stromal cells, act as immunosuppressors, and are among the key regulators of acute and chronic inflammation. The objective of this study was to determine if the level of the PD-1 ligands is changed in the IBD inflamed colonic mucosa and to test the hypothesis that changes in IBD-CMF-mediated PD-1 ligand-linked immunosuppression is a mechanism promoting the dysregulation of Th1 cell responses...
2018: Frontiers in Immunology
Chia-Ing Jan, Wan-Chen Tsai, Horng-Jyh Harn, Woei-Cherng Shyu, Ming-Chao Liu, Hsin-Man Lu, Shao-Chih Chiu, Der-Yang Cho
Background: Glioblastoma (GBM) is the most common and lethal primary malignant glioma in adults. Dendritic cell (DC) vaccines have demonstrated promising results in GBM clinical trials. However, some patients do not respond well to DC therapy, with survival rates similar to those of conventional therapy. We retrospectively analyzed clinical and laboratory data to evaluate the factors affecting vaccine treatment. Methods: Forty-seven patients with de novo GBM were enrolled at China Medical University Hospital between 2005 and 2010 and divided into two subgroups...
2018: Frontiers in Immunology
Aaron M Goodman, David Piccioni, Shumei Kato, Amélie Boichard, Huan-You Wang, Garrett Frampton, Scott M Lippman, Caitlin Connelly, David Fabrizio, Vincent Miller, Jason K Sicklick, Razelle Kurzrock
Importance: Copy number alterations in programmed cell death ligand 1 (PDL1 or CD274), programmed cell death 1 ligand 2 (PDCD1LG2 or PDL2), and Janus kinase 2 (JAK2) genes (chromosome 9p24.1) characterize Hodgkin lymphoma, resulting in high response rates to programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) blockade. The prevalence and utility of PDL1 amplification as a response biomarker to PD-1/PD-L1 blockade are unknown in other tumors. Objectives: To examine the prevalence of PDL1 amplification and its utility as a response biomarker to PD-1/PD-L1 blockade in solid tumors...
June 14, 2018: JAMA Oncology
Ashley Volaric, Ryan Gentzler, Richard Hall, James H Mehaffey, Edward B Stelow, Timothy N Bullock, Linda W Martin, Anne M Mills
The immune regulatory enzyme indoleamine-2,3-dioxygenase (IDO-1) suppresses T cell responses and may reduce efficacy of therapies targeting immune checkpoints such as programmed death receptor-1/programmed death ligand-1 (PD-1/PD-L1). Early phase clinical trials combining IDO-1 and PD-1/PD-L1 inhibitors have shown some promise in non-small cell lung cancers (NSCLCs). However, the coexpression of IDO-1 and PD-L1 has not been thoroughly investigated, and the potential for IDO-1 immunohistochemical expression as a therapeutic biomarker is unknown...
June 12, 2018: American Journal of Surgical Pathology
Tsuyoshi Hamada, Thing Rinda Soong, Yohei Masugi, Keisuke Kosumi, Jonathan A Nowak, Annacarolina da Silva, Xinmeng Jasmine Mu, Tyler S Twombly, Hideo Koh, Juhong Yang, Mingyang Song, Li Liu, Mancang Gu, Yan Shi, Katsuhiko Nosho, Teppei Morikawa, Kentaro Inamura, Sachet A Shukla, Catherine J Wu, Levi A Garraway, Xuehong Zhang, Kana Wu, Jeffrey A Meyerhardt, Andrew T Chan, Jonathan N Glickman, Scott J Rodig, Gordon J Freeman, Charles S Fuchs, Reiko Nishihara, Marios Giannakis, Shuji Ogino
Inhibitors targeting the PDCD1 (programmed cell death 1, PD-1) immune checkpoint pathway have revolutionized cancer treatment strategies. The TIME (Tumor Immunity in the MicroEnvironment) classification based on tumor CD274 ( PDCD1 ligand 1, PD-L1) expression and tumor-infiltrating lymphocytes (TIL) has been proposed to predict response to immunotherapy. It remains to be determined clinical, pathological, and molecular features of TIME subtypes of colorectal cancer. Using 812 colon and rectal carcinoma cases from the Nurses' Health Study and Health Professionals Follow-up Study, we examined the association of tumor characteristics and survival outcomes with four TIME subtypes (TIME 1, CD274 low /TILabsent ; TIME 2, CD274 high /TILpresent ; TIME 3, CD274 low /TILpresent ; and TIME 4, CD274 high /TILabsent )...
2018: Oncoimmunology
Yasunori Akutsu, Kentaro Murakami, Masayuki Kano, Takeshi Toyozumi, Yasunori Matsumoto, Masahiko Takahashi, Ryota Otsuka, Nobufumi Sekino, Masaya Yokoyama, Tadashi Shiraishi, Hisahiro Matsubara
BACKGROUND: We determined the serum concentrations of Programmed cell death-1 (PD-1) and its ligands (PD-L1 and PD-L2) in patients with esophageal squamous cell carcinoma (ESCC). METHODS: Blood samples were collected from 85 patients with histologically proved ESCC. Serum levels of PD-1, PD-L1, and PD-L2 were measured using enzyme linked immunosorbent assays. Correlations between serum PD-1, PD-L1, and PD-L2 concentration and tumor depth, number of lymph node metastases, organ metastasis status, or disease stage were assessed and five-year survival rates according to clinicopathological characteristics were calculated...
April 2018: Esophagus: Official Journal of the Japan Esophageal Society
Xiao-Ran Yu, Qiao-Sheng Wen, Yi Xiao, Rui Tang, Fu-Xi Li, Wen-Feng Shao, Yan-Lin Yu, Jing-Bo Xiong
OBJECTIVE: To study if programmed death-ligand 1 (PL-L1) expression in breast cancer cell activates PD-L1/PD-1 pathway in dendritic cells to inhibit dendritic cell maturation. METHODS: Human monocytes were induced to differentiate into immature dendritic cells using GM-CSF and IL-4, and further to mature dendritic cells using TNF-α. PD-L1-expressing breast cancer cell line MDA-MB-231 was co-cultured in contact with the dendritic cells to observe the effects of the breast cancer cells on the maturation of the dendritic cells...
May 20, 2018: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
Marina Kazantseva, Ramona A Eiholzer, Sunali Mehta, Ahmad Taha, Sara Bowie, Imogen Roth, Jean Zhou, Sebastien M Joruiz, Janice A Royds, Noelyn A Hung, Tania L Slatter, Antony W Braithwaite
As tumour protein 53 (p53) isoforms have tumour promoting, migration and inflammatory properties, this study investigated whether p53 isoforms contributed to glioblastoma progression. The expression levels of full-length TP53α (TAp53α) and six TP53 isoforms were quantitated by RT-qPCR in 89 glioblastomas and correlated with TP53 mutation status, tumour-associated macrophage content and various immune cell markers. Elevated levels of Δ133p53β mRNA characterised glioblastomas with increased CD163-positive macrophages and wild-type TP53...
June 10, 2018: Journal of Pathology
Azfar Neyaz, Nuzhat Husain, Swati Kumari, Sameer Gupta, Saumya Shukla, Sanya Arshad, Nidhi Anand, Arun Chaturvedi
INTRODUCTION: Gallbladder carcinoma has limited therapeutic options and a poor outcome with conventional therapy. Program death ligand (PD-L1) has been used as a potential target for immune checkpoint inhibitors in various solid neoplasms. PD-L1 expression has been studied in very few cases of gallbladder cancer. MATERIALS AND METHODS: 174 cases of gallbladder carcinoma were evaluated for PD-L1 expression using SP263 clone in tissue microarray. Clinico-pathological characteristics and survival data were correlated with PD-L1 expression analysed at different cut-offs of ≥1%, ≥10% and ≥50% in tumour cells and tumour infiltrating lymphocytes (TILs)...
June 8, 2018: Histopathology
Kohei Shitara, Mustafa Özgüroğlu, Yung-Jue Bang, Maria Di Bartolomeo, Mario Mandalà, Min-Hee Ryu, Lorenzo Fornaro, Tomasz Olesiński, Christian Caglevic, Hyun C Chung, Kei Muro, Eray Goekkurt, Wasat Mansoor, Raymond S McDermott, Einat Shacham-Shmueli, Xinqun Chen, Carlos Mayo, S Peter Kang, Atsushi Ohtsu, Charles S Fuchs
BACKGROUND: Patients with advanced gastric or gastro-oesophageal junction cancer that progresses on chemotherapy have poor outcomes. We compared pembrolizumab with paclitaxel in patients with advanced gastric or gastro-oesophageal junction cancer that progressed on first-line chemotherapy with a platinum and fluoropyrimidine. METHODS: This randomised, open-label, phase 3 study was done at 148 medical centres in 30 countries. Eligible patients were randomised (1:1) in blocks of four per stratum with an interactive voice-response and integrated web-response system to receive either pembrolizumab 200 mg every 3 weeks for up to 2 years or standard-dose paclitaxel...
June 4, 2018: Lancet
Jinrong Peng, Yao Xiao, Wenting Li, Qian Yang, Liwei Tan, Yanpeng Jia, Ying Qu, Zhiyong Qian
The therapeutic outcome of photothermal therapy (PTT) remains impeded by the transparent depth of light. Combining PTT with immunotherapy provides strategies to solve this problem. Regulating metabolism-related enzymes is a promising strategy to stimulate immune response. Here, a nanosystem (NLG919/IR780 micelles) with the properties of photothermal conversion and regulation of the tryptophan metabolic pathway is used to suppress the growth of the tumor margin beyond effective PTT and promote tumor PTT and immunotherapy...
May 2018: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
Na Luo, Luigi Formisano, Paula I Gonzalez-Ericsson, Violeta Sanchez, Phillip T Dean, Susan R Opalenik, Melinda E Sanders, Rebecca S Cook, Carlos L Arteaga, Douglas B Johnson, Justin M Balko
Immunotherapies targeting programmed cell death protein 1 (PD-1) or its ligand, programmed cell death ligand 1 (PD-L1), dramatically improve the survival of melanoma patients. However, only ∼40% of treated patients demonstrate a clinical response to single-agent anti-PD-1 therapy. An intact tumor response to type-II interferon (i.e. IFN-γ) correlates with response to anti-PD-1, and patients with de novo or acquired resistance may harbor loss-of-function alterations in the JAK/STAT pathway, which lies downstream of the interferon gamma receptor (IFNGR1/2)...
2018: Oncoimmunology
Edwin R Parra, Pamela Villalobos, Carmen Behrens, Mei Jiang, Apar Pataer, Stephen G Swisher, William N William, Jiexin Zhang, Jack Lee, Tina Cascone, John V Heymach, Marie-Andrée Forget, Cara Haymaker, Chantale Bernatchez, Neda Kalhor, Annikka Weissferdt, Cesar Moran, Jianjun Zhang, Ara Vaporciyan, Don L Gibbons, Boris Sepesi, Ignacio I Wistuba
BACKGROUND: The clinical efficacy observed with inhibitors of programed cell death 1/programed cell death ligand 1 (PD-L1/PD-1) in cancer therapy has prompted studies to characterize the immune response in several tumor types, including lung cancer. However, the immunological profile of non-small cell lung carcinoma (NSCLC) treated with neoadjuvant chemotherapy (NCT) is not yet fully characterized, and it may be therapeutically important. The aim of this retrospective study was to characterize and quantify PD-L1/PD-1 expression and tumor-associated immune cells (TAICs) in surgically resected NSCLCs from patients who received NCT or did not receive NCT (non-NCT)...
June 6, 2018: Journal for Immunotherapy of Cancer
Mohamed E Salem, Alberto Puccini, Joanne Xiu, Derek Raghavan, Heinz-Josef Lenz, W Michael Korn, Anthony F Shields, Philip A Philip, John L Marshall, Richard M Goldberg
BACKGROUND: Gastroesophageal cancers are often grouped together even though cancers that originate in the esophagus often exhibit different histological features, geographical distribution, risk factors, and clinical characteristics than those originating in the stomach. Herein, we aimed to compare the molecular characteristics of three different gastroesophageal cancer types: esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), and gastric adenocarcinoma (GAC)...
June 4, 2018: Oncologist
Jun Gong, Thang Q Le, Erminia Massarelli, Andrew E Hendifar, Richard Tuli
Several inhibitors of programmed cell death-1 (PD-1) and programmed death ligand-1 (PD-L1) have been approved as a form of immunotherapy for multiple cancers. Ionizing radiation therapy (RT) has been shown to enhance the priming and effector phases of the antitumor T-cell response rendering it an attractive therapy to combine with PD-1/PD-L1 inhibitors. Preclinical data support the rational combination of the 2 modalities and has paved way for the clinical development of the combination across a spectrum of cancers...
June 4, 2018: Journal for Immunotherapy of Cancer
Mark A Socinski, Robert M Jotte, Federico Cappuzzo, Francisco Orlandi, Daniil Stroyakovskiy, Naoyuki Nogami, Delvys Rodríguez-Abreu, Denis Moro-Sibilot, Christian A Thomas, Fabrice Barlesi, Gene Finley, Claudia Kelsch, Anthony Lee, Shelley Coleman, Yu Deng, Yijing Shen, Marcin Kowanetz, Ariel Lopez-Chavez, Alan Sandler, Martin Reck
Background The cancer-cell-killing property of atezolizumab may be enhanced by the blockade of vascular endothelial growth factor-mediated immunosuppression with bevacizumab. This open-label, phase 3 study evaluated atezolizumab plus bevacizumab plus chemotherapy in patients with metastatic nonsquamous non-small-cell lung cancer (NSCLC) who had not previously received chemotherapy. Methods We randomly assigned patients to receive atezolizumab plus carboplatin plus paclitaxel (ACP), bevacizumab plus carboplatin plus paclitaxel (BCP), or atezolizumab plus BCP (ABCP) every 3 weeks for four or six cycles, followed by maintenance therapy with atezolizumab, bevacizumab, or both...
June 4, 2018: New England Journal of Medicine
P Li, Y-Y Zhang, J Deng
OBJECTIVE: We investigated the effects of BMSCs, which was modified by programmed death ligand-1 immunoglobulin (PDL1Ig) gene, on the immunological rejection of orthotopic liver transplantation (OLT) in rats. MATERIALS AND METHODS: Rat BMSCs were cultured and modified by recombinant adenovirus pAdEasy-1/PDL1Ig for 72h. The total protein was extracted, and the protein expression of PDL1Ig after transfection was detected by Western blotting. Mixed lymphocyte reaction was applied to detect the inhibitory effect of BMSCs, including pre-transfection and post-transfection, on the cell activity of T lymphocytes in peripheral blood...
May 2018: European Review for Medical and Pharmacological Sciences
Xiao Yang, Guoxing Zhu, Zhengjie Yang, Ke Zeng, Fengxiang Liu, Junying Sun
PURPOSE: Chondrosarcoma is a malignancy affecting cartilage and is chemo- and radio-resistant. Novel immune checkpoint inhibitors may play a role in treatment; however, expression of programmed cell death ligand 1/2 (PD-L1/PD-L2) in chondrosarcoma is unreported. METHODS: Chondrosarcoma sections were collected and stained immunohistochemically for PD-L1, PD-L2, Ki-67, and TP53. Clinicopathological parameters were collected and analyzed statistically for associations and correlations...
May 1, 2018: International Journal of Biological Markers
Shiqiong Xu, Hong Yu, Guohui Fu, Xianqun Fan, Renbing Jia
PURPOSE: A limited number of therapies are available for patients with metastatic eyelid sebaceous carcinoma (SC). Programmed death receptor Ligand 1 (PD-L1) expression and its clinical significance in sebaceous cell carcinoma are presently unknown. This study aimed to evaluate the expression level of PD-L1 in SC. METHODS: This single centre, retrospective, and comparative study was conducted at the Ninth People's Hospital between August 1, 2013 and September 1, 2016...
June 4, 2018: Acta Ophthalmologica
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