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https://www.readbyqxmd.com/read/29225343/advances-in-the-understanding-and-treatment-of-sepsis-induced-immunosuppression
#1
REVIEW
Fabienne Venet, Guillaume Monneret
Sepsis is defined as a life-threatening organ dysfunction that is caused by a dysregulated host response to infection. Sepsis can induce acute kidney injury and multiple organ failures and represents the most common cause of death in the intensive care unit. Sepsis initiates a complex immune response that varies over time, with the concomitant occurrence of both pro-inflammatory and anti-inflammatory mechanisms. As a result, most patients with sepsis rapidly display signs of profound immunosuppression, which is associated with deleterious consequences...
December 11, 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/29192247/immunotherapy-pdl1-restoration-reverses-t1dm
#2
Conor A Bradley
No abstract text is available yet for this article.
December 1, 2017: Nature Reviews. Endocrinology
https://www.readbyqxmd.com/read/29180488/rhesus-macaque-myeloid-derived-suppressor-cells-demonstrate-t-cell-inhibitory-functions-and-are-transiently-increased-after-vaccination
#3
Ang Lin, Frank Liang, Elizabeth A Thompson, Maria Vono, Sebastian Ols, Gustaf Lindgren, Kimberly Hassett, Hugh Salter, Giuseppe Ciaramella, Karin Loré
Myeloid-derived suppressor cells (MDSCs) are major regulators of T cell responses in several pathological conditions. Whether MDSCs increase and influence T cell responses in temporary inflammation, such as after vaccine administration, is unknown. Using the rhesus macaque model, which is critical for late-stage vaccine testing, we demonstrate that monocytic (M)-MDSCs and polymorphonuclear (PMN)-MDSCs can be detected using several of the markers used in humans. However, whereas rhesus M-MDSCs lacked expression of CD33, PMN-MDSCs were identified as CD33+ low-density neutrophils...
November 27, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29174566/the-roles-of-pathology-in-targeted-therapy-of-women-with-gynecologic-cancers
#4
Rajmohan Murali, Rachel N Grisham, Robert A Soslow
The role of the pathologist in the multidisciplinary management of women with gynecologic cancer has evolved substantially over the past decade. Pathologists' evaluation of parameters such as pathologic stage, histologic subtype, grade and microsatellite instability, and their identification of patients at risk for Lynch syndrome have become essential components of diagnosis, prognostic assessment and determination of optimal treatment of affected women. Despite the use of multimodality treatment and combination cytotoxic chemotherapy, the prognosis of women with advanced-stage gynecologic cancer is often poor...
November 23, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/29150702/high-pdl1-mrna-expression-predicts-better-survival-of-stage-pt1-non-muscle-invasive-bladder-cancer-nmibc-patients
#5
Johannes Breyer, Ralph M Wirtz, Wolfgang Otto, Philipp Erben, Thomas S Worst, Robert Stoehr, Markus Eckstein, Stefan Denzinger, Maximilian Burger, Arndt Hartmann
INTRODUCTION AND OBJECTIVES: Checkpoint inhibition has emerged as new therapeutic option in muscle-invasive bladder cancer. The objective of the present study was to evaluate the prognostic role of PD1 and PDL1 expression in non-muscle-invasive bladder cancer (NMIBC) and establish an objective measuring method using RNA quantification. MATERIALS AND METHODS: We retrospectively analyzed clinical data and formalin-fixed paraffin-embedded tissues (FFPE) of patients with stage pT1 NMIBC who underwent transurethral resection of the bladder...
November 17, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29146060/clinicopathologic-correlation-of-programmed-death-ligand-1-expression-in-non-small-cell-lung-carcinomas-a-report-from-india
#6
Archana George Vallonthaiel, Prabhat Singh Malik, Varsha Singh, Vinay Kumar, Sunil Kumar, Mehar Chand Sharma, Sandeep Mathur, Sudheer Arava, Randeep Guleria, Deepali Jain
INTRODUCTION: Increased expression of Programmed death ligand-1 (PD-L1) on cancer cells and immune cells predict response to PD-1/PDL1 inhibitors. Data regarding frequency and pattern of PD-L1 expression in NSCLC from India is not available. OBJECTIVES: To analyse PD-L1 expression on tumour cells (TC) and immune cells (IC) and to correlate PD-L1 expression with baseline clinico-pathological characteristics, oncogenic drivers and outcome data. MATERIALS AND METHODS: PD-L1 expression on tumour cells and immune cells was analysed...
December 2017: Annals of Diagnostic Pathology
https://www.readbyqxmd.com/read/29137398/prognostic-significance-of-pd-l1-expression-and-tumor-infiltrating-lymphocyte-in-surgically-resectable-non-small-cell-lung-cancer
#7
Gen Lin, Xirong Fan, Weifeng Zhu, Cheng Huang, Wu Zhuang, Haipeng Xu, Xiandong Lin, Dan Hu, Yunjian Huang, Kan Jiang, Qian Miao, Chao Li
Programmed death ligand 1 (PD-L1) expression is a predictive biomarker of the success of PD-1/PD-L1 inhibitor therapy for patients with advanced non-small cell lung cancer (NSCLC) but its role as a prognostic marker for early stage resectable NSCLC remains unclear. Here, we studied PD-L1 expression and tumor infiltrating lymphocytes (TILs) in surgically resectable NSCLC and correlate the finding with clinicopathological features and patient outcomes. Total of 170 archival samples of resectable NSCLC were probed for PD-L1 expression using the clone 22C3 pharmDx kit...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29133939/precision-medicine-for-urothelial-bladder-cancer-update-on-tumour-genomics-and-immunotherapy
#8
REVIEW
Kenneth M Felsenstein, Dan Theodorescu
Effective management of advanced urothelial bladder cancer is challenging. New discoveries that improve our understanding of molecular bladder cancer subtypes have revealed numerous potentially targetable genomic alterations and demonstrated the efficacy of treatments that harness the immune system. These findings have begun to change paradigms of bladder cancer therapy. For example, DNA repair pathway mutations in genes such as ERCC2, FANCC, ATM, RB1, and others can predict responses to neoadjuvant platinum-based chemotherapies and to targeted therapies on the basis of mutation status...
November 14, 2017: Nature Reviews. Urology
https://www.readbyqxmd.com/read/29132694/unrelated-immunodeficiency-states-may-impact-outcomes-and-immune-checkpoint-molecule-expression-in-patients-with-mycosis-fungoides-a-clinicopathologic-case-control-study
#9
Shay Warren, Meenal Kheterpal, Patricia L Myskowski, Alison Moskowitz, Steven M Horwitz, Melissa P Pulitzer
BACKGROUND: Immunodeficiency (ID) correlates with worse outcomes and decreased immune checkpoint molecule expression in melanoma. The impact of ID in mycosis fungoides (MF) is unknown. OBJECTIVE: Our goal was to evaluate the impact of ID in MF. METHODS: We conducted a case-control study of 17 patients with MF and ID versus age-, stage-, and race-matched controls as a subset of a comparative analysis of 23 patients with MF with ID (prior lymphoma, recent/current pregnancy, HIV, hypogammaglobulinemia, and prior chemotherapy) versus without ID...
November 10, 2017: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/29114543/molecular-mechanisms-of-programmed-cell-death-1-dependent-t-cell-suppression-relevance-for-immunotherapy
#10
REVIEW
Miren Zuazo, Maria Gato-Cañas, Noelia Llorente, María Ibañez-Vea, Hugo Arasanz, Grazyna Kochan, David Escors
Programmed cell death-1 (PD1) has become a significant target for cancer immunotherapy. PD1 and its receptor programmed cell death 1 ligand 1 (PDL1) are key regulatory physiological immune checkpoints that maintain self-tolerance in the organism by regulating the degree of activation of T and B cells amongst other immune cell types. However, cancer cells take advantage of these immunosuppressive regulatory mechanisms to escape T and B cell-mediated immunity. PD1 engagement on T cells by PDL1 on the surface of cancer cells dramatically interferes with T cell activation and the acquisition of effector capacities...
October 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/29096940/anti-pd1-pdl1-induced-psoriasis
#11
Dimitra Voudouri, Vasiliki Nikolaou, Konstantinos Laschos, Andriani Charpidou, Nikolaos Soupos, Ioanna Triantafyllopoulou, Ioanna Panoutsopoulou, Gerasimos Aravantinos, K Syrigos, A Stratigos
BACKGROUND: Immune checkpoint inhibitors are novel agents approved for the treatment of late-stage malignancies. Despite its important clinical benefits, checkpoint inhibition is associated with a unique spectrum of side effects known as immune-related adverse events. Skin toxicities are the most frequent immune-related adverse events during anti-PD1 blockade therapies. Among them, rare cases of psoriasis exacerbation have been reported. METHODS: We present the clinical characteristics of exacerbated psoriasis in 5 patients under anti-PD1/PDL1 therapy...
October 18, 2017: Current Problems in Cancer
https://www.readbyqxmd.com/read/29084057/evaluation-of-pd1-pdl1-expression-and-their-clinicopathologic-association-in-ebv-associated-lymphoproliferative-disorders-in-nonimmunosuppressed-patients
#12
Ling Guo, Juraj Bodo, Lisa Durkin, Eric D Hsi
Epstein-Barr virus (EBV)-associated lymphoproliferative disorders (LPD)/lymphomas in nonimmunosuppressed patients represent a unique entity and have been proposed to be related to immune senescence. Engagement of programmed cell death 1 (PD1) by its ligand programmed death ligand 1 (PDL1) inhibits T-cell activation, and leads to T-cell exhaustion. In clinical trials, therapeutic antibodies that block the PD1-PDL1 axis have shown promising therapeutic activity in certain types of lymphomas. Although PD1/PDL1 has been extensively studied in variety of lymphomas, there are few reports characterizing their expression in EBV-positive LPD...
October 27, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/29070073/the-dose-of-hbv-genome-contained-plasmid-has-a-great-impact-on-hbv-persistence-in-hydrodynamic-injection-mouse-model
#13
Lei Li, Sheng Li, Yun Zhou, Lu Yang, Di Zhou, Yan Yang, Mengji Lu, Dongliang Yang, Jingjiao Song
BACKGROUND: Hydrodynamic injection (HI) of hepatitis B virus (HBV) mouse model is an useful tool for HBV related research in vivo. However, only 40% of C57/BL6 mice injected with 10 μg HBV genome contained plasmid (pAAV-HBV1.2), serum HBsAg more than 6 months and none of the BALB/c mice injected with 10 μg pAAV-HBV1.2 plasmid DNA, serum HBsAg positive more than 4 weeks in the previous study. METHODS: In this study, C57/BL6 and BALB/c mice were hydrodynamic injected with different doses of pAAV-HBV1...
October 25, 2017: Virology Journal
https://www.readbyqxmd.com/read/29066622/microrna-155-induction-via-tnf-%C3%AE-and-ifn-%C3%AE-suppresses-expression-of-programmed-death-ligand-1-pd-l1-in-human-primary-cells
#14
Daniel Yee, Kunal M Shah, Mark C Coles, Tyson V Sharp, Dimitris Lagos
Programmed death ligand-1 (PD-L1) is a critical regulator of T cell function contributing to peripheral immune tolerance. Although it has been shown that posttranscriptional regulatory mechanisms control PD-L1 expression in cancer, it remains unknown whether such regulatory loops operate also in non-transformed cells. Here we studied PD-L1 expression in human dermal lymphatic endothelial cells (HDLECs), which play key roles in immunity and cancer. Treatment of HDLECs with the pro-inflammatory cytokines IFN-γ and TNF-α synergistically upregulated PDL1 expression...
October 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29059149/targeting-immunosuppressive-adenosine-in-cancer
#15
REVIEW
Dipti Vijayan, Arabella Young, Michele W L Teng, Mark J Smyth
Despite the success of anti-programmed cell death protein 1 (PD1), anti-PD1 ligand 1 (PDL1) and anti-cytotoxic T lymphocyte antigen 4 (CTLA4) therapies in advanced cancer, a considerable proportion of patients remain unresponsive to these treatments (known as innate resistance). In addition, one-third of patients relapse after initial response (known as adaptive resistance), which suggests that multiple non-redundant immunosuppressive mechanisms coexist within the tumour microenvironment. A major immunosuppressive mechanism is the adenosinergic pathway, which now represents an attractive new therapeutic target for cancer therapy...
October 23, 2017: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/29057919/identification-and-validation-of-a-pd-l1-binding-peptide-for-determination-of-pdl1-expression-in-tumors
#16
Charles Caldwell, Cory E Johnson, V N Balaji, Govardhan A Balaji, Richard D Hammer, Raghuraman Kannan
Blocking the interaction between Programmed Death Ligand 1 (PD-L1) and its receptor, PD-1, is an effective method of treating many types of cancers. Certain tumors overexpress PD-L1, causing host immune cells that express PD-1 to bind PD-L1 and cease killing the tumor. Inhibition of PD-L1 and PD-1 binding can restore host immunity towards tumor killing, and many new drugs have been developed to target this interaction. Current methods of PD-L1 diagnosis have shown to vary based on the antibody, detection kit brand, antigen retrieval method, and clinically defined methods by the FDA...
October 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29053414/perk-phosphorylated-eif2%C3%AE-pathway-suppresses-tumor-metastasis-through-downregulating-expression-of-programmed-death-ligand-1-and-cxcl5-in-triple-negative-breast-cancer
#17
Weiwei Zou, Yu Bai, Xilong Wang, Kai Cheng, Hongguang Sun, Guoqiang Zhang, Xiaohong Wang, Zhenlin Yang
Endoplasmic reticulum (ER) stress has been reported to be associated with metastasis in many malignant tumors. PKR-like ER kinase-phosphorylated eukaryotic translation initiation factor 2α (PERK-p-eIF2α) pathway is one of the three main signal pathways in ER stress, however, its mechanism in regulating breast cancer (BC) relapse or metastasis was still not completely understood. Besides, drug resistance was an important factor influencing the effect of tumor treatment and whether PERK-p-eIF2α pathway was involved in the drug resistance to BC treatment also needs to be explored...
October 2017: Cancer Biotherapy & Radiopharmaceuticals
https://www.readbyqxmd.com/read/29043842/the-protective-and-immunomodulatory-effects-of-fucoidan-against-7-12-dimethyl-benz-a-anthracene-induced-experimental-mammary-carcinogenesis-through-the-pd1-pdl1-signaling-pathway-in-rats
#18
Meilan Xue, Hui Liang, Qingjuan Tang, Chuanxing Xue, Xinjia He, Li Zhang, Zheng Zhang, Zhengyan Liang, Kang Bian, Lichen Zhang, Zhuxin Li
Fucoidan is a sulfated polysaccharide that is extracted from brown algae seaweed. This study was designed to evaluate the protective and immunomodulatory effects of dietary fucoidan on 7,12-dimethyl benz[a]anthracene (DMBA)-induced experimental mammary carcinogenesis in rats. Sixty Sprague-Dawley rats were randomly assigned to four equal groups: the control group (control group), the cancer model group (model group), and the F1 and F2 groups, which were fed fucoidan at concentrations of 200 and 400 mg/kg·body weight, respectively...
October 18, 2017: Nutrition and Cancer
https://www.readbyqxmd.com/read/29016555/interleukin-10-regulated-tumour-tolerance-in-non-small-cell-lung-cancer
#19
Julius Malte Vahl, Juliane Friedrich, Susanne Mittler, Sonja Trump, Lisanne Heim, Katerina Kachler, Liubov Balabko, Nicole Fuhrich, Carol-Immanuel Geppert, Denis Iulian Trufa, Nina Sopel, Ralf Rieker, Horia Sirbu, Susetta Finotto
BACKGROUND: Lung cancer is the most life-threatening cancer type worldwide. Treatment options include surgery, radio- and chemotherapy, as well as the use of immunomodulatory antibodies. Interleukin (IL)-10 is an immunosuppressive cytokine involved in tumour immune escape. METHODS: Immunohistochemistry (IHC) on human lung surgery tissue as well as human tumour cell line cultures, FACS analysis, real-time PCR and experimental lung cancer. RESULTS: Here we discovered a positive correlation between IL-10 and IL-10 receptor (IL-10R) expression in the lung with tumour diameter in patients with lung cancer (non-small cell lung cancer), the most life-threatening cancer type worldwide...
October 10, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28974431/adenovirotherapy-delivering-cytokine-and-checkpoint-inhibitor-augments-car-t-cells-against-metastatic-head-and-neck-cancer
#20
Amanda Rosewell Shaw, Caroline E Porter, Norihiro Watanabe, Kiyonori Tanoue, Andrew Sikora, Stephen Gottschalk, Malcolm K Brenner, Masataka Suzuki
In solid tumors, chimeric antigen receptor (CAR)-modified T cells must overcome the challenges of the immunosuppressive tumor microenvironment. We hypothesized that pre-treating tumors with our binary oncolytic adenovirus (CAd), which produces local oncolysis and expresses immunostimulatory molecules, would enhance the antitumor activity of HER2-specific CAR T cells, which alone are insufficient to cure solid tumors. We tested multiple cytokines in conjunction with PD-L1-blocking antibody and found that Ad-derived IL-12p70 prevents the loss of HER2...
November 1, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
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