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https://www.readbyqxmd.com/read/29679564/frequencies-and-expression-levels-of-programmed-death-ligand-1-pd-l1-in-circulating-tumor-rna-ctrna-in-various-cancer-types
#1
Toshiyuki Ishiba, Andreas-Claudius Hoffmann, Joshua Usher, Yahya Elshimali, Todd Sturdevant, Mai Dang, Yolanda Jaimes, Rama Tyagi, Ronald Gonzalez, Mary Grino, Jacek K Pinski, Afsaneh Barzi, Luis E Raez, Wilfried E Eberhardt, Dirk Theegarten, Heinz-Josef Lenz, Hiroyuki Uetake, Peter V Danenberg, Kathleen Danenberg
BACKGROUND: Precision medicine and prediction of therapeutic response requires monitoring potential biomarkers before and after treatment. Liquid biopsies provide noninvasive prognostic markers such as circulating tumor DNA and RNA. Circulating tumor RNA (ctRNA) in blood is also used to identify mutations in genes of interest, but additionally, provides information about relative expression levels of important genes. In this study, we analyzed PD-L1 expression in ctRNA isolated from various cancer types...
April 18, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29679556/a-novel-smac-mimetic-apg-1387-exhibited-dual-antitumor-effect-on-hbv-positive-hepatocellular-carcinoma-with-high-expression-of-ciap2-by-inducing-apoptosis-and-enhancing-innate-anti-tumor-immunity
#2
Wentao Pan, Qiuyun Luo, Xianglei Yan, Luping Yuan, Hanjie Yi, Lin Zhang, Baoxia Li, Yuxin Zhang, Jian Sun, Miao-Zhen Qiu, Da-Jun Yang
Check point inhibitor anti-PD1 antibody produced some efficacy in Hepatocellular Carcinoma (HCC) patients previously treated with sorafenib. Unfortunately, HCC patients with hepatitis B virus (HBV) infection did not respond as well as uninfected patients. Previously, SMAC mimetics-the antagonist for inhibitor of apoptosis proteins (IAPs) can rapidly reduce serum hepatitis B virus DNA in animal model. APG-1387 is a novel SMAC-mimetic, small molecule inhibitor targeting inhibitor of apoptosis proteins (IAPs)...
April 18, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29675979/senescent-cells-re-engineered-to-express-spd-1-for-inhibiting-pd-1-pd-l1-as-a-vaccination-approach-against-breast-cancer
#3
Zehong Chen, Kang Hu, Lieting Feng, Ruxiong Su, Nan Lai, Zike Yang, Shijun Kang
Various types of vaccines have been proposed as approaches for prevention or delay of the onset of cancer by boosting the endogenous immune system. We previously developed a senescent-cell-based vaccine, induced by radiation and veliparib, as a preventive and therapeutic tool against triple-negative breast cancer. However, the PD-1/PD-L1 pathway was found to play an important role in vaccine failure. Hence, we further developed sPD1-expressing senescent cells to overcome PD-L1/PD1-mediated immune suppression while vaccinating to promote dendritic cells (DCs) maturity, thereby amplifying T cell activation...
April 20, 2018: Cancer Science
https://www.readbyqxmd.com/read/29670614/human-v%C3%AE-9v%C3%AE-2-t-cells-synergize-cd4-t-follicular-helper-cells-to-produce-influenza-virus-specific-antibody
#4
Qingyun Chen, Kun Wen, Aizhen Lv, Ming Liu, Ke Ni, Zheng Xiang, Yinping Liu, Wenwei Tu
Human Vγ9Vδ2-T cells recognize nonpeptidic antigens and exert effector functions against microorganisms and tumors, but little is known about their roles in humoral immune response against influenza virus infection. Herein, in the coculture of autologous human B cells, dendritic cells and/or naïve CD4 T cells, and Vγ9Vδ2-T cells, we demonstrated that Vγ9Vδ2-T cells could facilitate H9N2 influenza virus-specific IgG and IgM productions in a CD4 T cell-dependent manner. Vγ9Vδ2-T cells promoted the differentiation of CXCR5+ PD1+ CD4+ T follicular helper (Tfh) cells, CD19+ IgD- CD38++ plasma cells (PCs), and drove B cell proliferation as well as immunoglobulin class switching...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29669806/targeting-merkel-cell-carcinoma-by-engineered-t-cells-specific-to-t-antigens-of-merkel-cell-polyomavirus
#5
Ioannis Gavvovidis, Matthias Leisegang, Gerald Willimsky, Natalie J Miller, Paul Nghiem, Thomas Blankenstein
PURPOSE: The causative agent of most cases of Merkel cell carcinoma (MCC) has been identified as the Merkel cell polyomavirus (MCV). MCV-encoded T-antigens (Tags) are essential not only for virus-mediated tumorigenesis but also for maintaining MCC cell lines in vitro. MCV Tags are thus an appealing target for viral oncoprotein-directed T cell therapy for MCC. With this study, we aimed to isolate and characterize Tag-specific T cell receptors (TCR) for potential use in gene therapy clinical trials...
April 18, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29669604/confirm-a-double-blind-placebo-controlled-phase-iii-clinical-trial-investigating-the-effect-of-nivolumab-in-patients-with-relapsed-mesothelioma-study-protocol-for-a-randomised-controlled-trial
#6
Dean A Fennell, Emma Kirkpatrick, Kelly Cozens, Mavis Nye, Jason Lester, Gerard Hanna, Nicola Steele, Peter Szlosarek, Sarah Danson, Joanne Lord, Christian Ottensmeier, Daniel Barnes, Stephanie Hill, Mihalis Kalevras, Tom Maishman, Gareth Griffiths
BACKGROUND: Mesothelioma is an incurable, apoptosis-resistant cancer caused in most cases by previous exposure to asbestos and is increasing in incidence. It represents a growing health burden but remains under-researched, with limited treatment options. Early promising signals of activity relating to both PD-L1- and PD-1-targeted treatment in mesothelioma implicate a dependency of mesothelioma on this immune checkpoint. There is a need to evaluate checkpoint inhibitors in patients with relapsed mesothelioma where treatment options are limited...
April 18, 2018: Trials
https://www.readbyqxmd.com/read/29669244/better-together-b7s1-checkpoint-blockade-synergizes-with-anti-pd1
#7
Melissa A Meyer, David G DeNardo
T cell checkpoint blockades can produce durable clinical responses, but only some patients and cancer types respond. In this issue of Immunity, Li et al. (2018) show B7S1-B7S1R signaling additionally regulates CD8+ T cell responses by working with the PD1-PDL1 checkpoint to block anti-tumor immunity.
April 17, 2018: Immunity
https://www.readbyqxmd.com/read/29665659/suppressive-effect-of-4-hydroxy-2-4-hydroxyphenethyl-isoindoline-1-3-dione-on-ovalbumin-induced-allergic-asthma
#8
Jin Huang, Mingzhi Su, Bo-Kyung Lee, Mee-Jeong Kim, Jee H Jung, Dong-Soon Im
4-Hydroxy-2-(4-hydroxyphenethyl)isoindoline-1,3-dione (PD1) is a synthetic phthalimide derivative of a marine compound. PD1 has peroxisome proliferator-activated receptor (PPAR) γ agonistic and anti-inflammatory effects. This study aimed to investigate the effect of PD1 on allergic asthma using rat basophilic leukemia (RBL)-2H3 mast cells and an ovalbumin (OVA)-induced asthma mouse model. In vitro , PD1 suppressed β-hexosaminidase activity in RBL-2H3 cells. In the OVA-induced allergic asthma mouse model, increased inflammatory cells and elevated Th2 and Th1 cytokine levels were observed in bronchoalveolar lavage fluid (BALF) and lung tissue...
April 18, 2018: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/29650750/braf-and-mek-inhibitors-increase-pd1-positive-melanoma-cells-leading-to-a-potential-lymphocyte-independent-synergism-with-anti-pd1-antibody
#9
Martina Sanlorenzo, Igor Vujic, Arianna Floris, Mauro Novelli, Loretta Gammaitoni, Lidia Giraudo, Marco Macagno, Valeria Leuci, Ramona Rotolo, Chiara Donini, Marco Basiricò, Pietro Quaglino, Maria Teresa Fierro, Silvia Giordano, Maria Sibilia, Fabrizio Carnevale-Schianca, Massimo Aglietta, Dario Sangiolo
PURPOSE: BRAF and MEK inhibitors (BRAF/MEKi) favor melanoma-infiltrating lymphocytes, providing the rationale for current combinatorial trials with anti-PD1 antibody. A portion of melanoma cells may express PD1, and anti-PD1 antibody could have a direct anti-tumor effect. Here, we explore if BRAF/MEKi modulate rates of PD1+ melanoma cells, supporting an additional - lymphocyte-independent - basis for their therapeutic combination with anti-PD1 antibody. EXPERIMENTAL DESIGN: With data mining and flow cytometry, we assessed PD1, PDL1/2 expression on melanoma cell lines (CCLE, N=61; validation cell lines, N=7) and melanoma tumors (TCGA, N=214)...
April 12, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29650641/anti-pd1-associated-fulminant-myocarditis-after-a-single-pembrolizumab-dose-the-role-of-occult-pre-existing-autoimmunity
#10
Nicolas Martinez-Calle, Paula Rodriguez-Otero, Sara Villar, Luis Mejías, Ignacio Melero, Felipe Prosper, Patricia Marinello, Bruno Paiva, Miguel Idoate, Jesus San-Miguel
No abstract text is available yet for this article.
April 12, 2018: Haematologica
https://www.readbyqxmd.com/read/29650143/perioperative-immunotherapy-in-muscle-invasive-bladder-cancer-and-upper-tract-urothelial-carcinoma
#11
REVIEW
Min Yuen Teo, Jonathan E Rosenberg
Neoadjuvant chemotherapy improves survival in patients with muscle-invasive bladder cancer. However, a significant proportion of patients are ineligible for cisplatin owing to renal impairment or other medical comorbidities. The introduction of anti-programmed cell death protein 1/programmed death-ligand 1(PD1/PD-L1) checkpoint inhibitors has redefined the therapeutic landscape for platinum-resistant urothelial cancers; their clinical efficacy and favorable toxicity render these agents attractive therapeutic options either as monotherapy or in combination with other agents in earlier disease states, including muscle-invasive disease...
May 2018: Urologic Clinics of North America
https://www.readbyqxmd.com/read/29648813/small-molecule-neuropilin-1-antagonists-combine-anti-angiogenic-and-anti-tumour-activity-with-immune-modulation-through-reduction-of-transforming-growth-factor-beta-tgf%C3%AE-production-in-regulatory-t-cells
#12
Jonathan Powell, Filipa Mota, David Steadman, Christelle Soudy, Jeremy T Miyauchi, Stuart Crosby, Ashley Jarvis, Tifelle Reisinge, Natalie Winfield, Graham Evans, Aled Finniear, Tamas Yelland, Yi-Tai Chou, A W Edith Chan, Andrew O'Leary, Lili Cheng, Dan Liu, Ntina Fotinou, Carla Milagre, John F Martin, Haiyan Jia, Paul Frankel, Snezana Djordjevic, Stella E Tsirka, Ian C Zachary, David L Selwood
We report the design, synthesis and comprehensive studybiological evaluation of a range ofsome potent small-molecule neuropilin-1 (NRP1) antagonists. NRP1 is implicated in the immune response to tumours, particularly in Treg cell fragility, required for PD1 checkpoint blockade. The design of these compounds was based on a previously identified compound EG00229, EG00229 which was used a starting point for optimisation. Through targeting of specific amino-acid residues additional H-bonding interactions were introduced, which led to increases in binding affinity and potency...
April 12, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29645384/liquid-biopsy-zur-%C3%A3-berwachung-von-melanompatienten
#13
REVIEW
Maria Rita Gaiser, Nikolas von Bubnoff, Christoffer Gebhardt, Jochen Sven Utikal
In den letzten sechs Jahren wurden verschiedene innovative systemische Therapien zur Behandlung des metastasierten malignen Melanoms (MM) entwickelt. Die konventionelle Chemotherapie wurde durch neuartige Primärtherapien abgelöst, darunter systemische Immuntherapien (Anti-CTLA4- und Anti-PD1-Antikörper; Zulassung von Anti-PDL1-Antikörpern erwartet) und Therapien, die gegen bestimmte Mutationen gerichtet sind (BRAF, NRAS und c-KIT). Daher stehen die behandelnden Ärzte neuen Herausforderungen gegenüber, beispielsweise der Stratifizierung von Patienten für geeignete Behandlungen und der Überwachung von Langzeit-Respondern auf Progression...
April 2018: Journal der Deutschen Dermatologischen Gesellschaft, Journal of the German Society of Dermatology: JDDG
https://www.readbyqxmd.com/read/29643229/t-cell-induced-csf1-promotes-melanoma-resistance-to-pd1-blockade
#14
Natalie J Neubert, Martina Schmittnaegel, Natacha Bordry, Sina Nassiri, Noémie Wald, Christophe Martignier, Laure Tillé, Krisztian Homicsko, William Damsky, Hélène Maby-El Hajjami, Irina Klaman, Esther Danenberg, Kalliopi Ioannidou, Lana Kandalaft, George Coukos, Sabine Hoves, Carola H Ries, Silvia A Fuertes Marraco, Periklis G Foukas, Michele De Palma, Daniel E Speiser
Colony-stimulating factor 1 (CSF1) is a key regulator of monocyte/macrophage differentiation that sustains the protumorigenic functions of tumor-associated macrophages (TAMs). We show that CSF1 is expressed in human melanoma, and patients with metastatic melanoma have increased CSF1 in blood compared to healthy subjects. In tumors, CSF1 expression correlated with the abundance of CD8+ T cells and CD163+ TAMs. Human melanoma cell lines consistently produced CSF1 after exposure to melanoma-specific CD8+ T cells or T cell-derived cytokines in vitro, reflecting a broadly conserved mechanism of CSF1 induction by activated CD8+ T cells...
April 11, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/29615718/genetic-abrogation-of-immune-checkpoints-in-antigen-specific-cytotoxic-t-lymphocyte-as-a-potential-alternative-to-blockade-immunotherapy
#15
Chi Zhang, Yanchun Peng, Philip Hublitz, Haokang Zhang, Tao Dong
T cell function can be compromised during chronic infections or through continuous exposure to tumor antigens by the action of immune checkpoint receptors, such as programmed cell death protein 1 (PD-1). Systemic administration of blocking antibodies against the PD-1 pathway can restore T cell function, and has been approved for the treatment of several malignancies, although there is a risk of adverse immune-related side-effects. We have developed a method for generating gene knockouts in human antigen (Ag)-specific cytotoxic T-Lymphocyte (CTLs) using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) genome editing...
April 3, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29615076/use-of-the-tumor-infiltrating-cd8-to-foxp3-lymphocyte-ratio-in-predicting-treatment-responses-to-combination-therapy-with-pertuzumab-trastuzumab-and-docetaxel-for-advanced-her2-positive-breast-cancer
#16
Koji Takada, Shinichiro Kashiwagi, Wataru Goto, Yuka Asano, Katsuyuki Takahashi, Tsutomu Takashima, Shuhei Tomita, Masahiko Ohsawa, Kosei Hirakawa, Masaichi Ohira
BACKGROUND: The trastuzumab, pertuzumab, and docetaxel (TPD) regimen is strongly recommended as a treatment option for first-line therapy for advanced human epidermal growth factor receptor (HER) 2-positive breast cancer. Monitoring the host microenvironments in cancer plays a significant role in predicting prognoses and curative effects. It is important to clarify the role of immune related gene expression in tumor-infiltrating lymphocytes in the tumor microenvironment. In this study, we evaluated the impact of chemotherapy with a TPD regimen, on immune micro environments in HER2-positive breast cancer using immune related proteins as indicators...
April 3, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29610255/pdl-1-blockade-prevents-t-cell-exhaustion-inhibits-autophagy-and-promotes-clearance-of-leishmania-donovani
#17
Samar Habib, Abdeljabar El Andaloussi, Khaled Elmasry, Aya Handoussa, Manar Azab, Aliaa Elsawey, Ayman Al-Hendy, Nahed Ismail
Leishmania donovani ( L. donovani ) is a causative pathogen of potentially-fatal visceral leishmaniasis (VL). Therapeutic agents are available; however, their use is limited due to high cost, serious side effects, and development of antimicrobial resistance. Protective immunity against VL depends on CD4+ Th1 cell-mediated immunity. Studies have shown that progression of VL is due to exhaustion of T cells; however, the mechanism involved is not clearly understood. Here, we examined the role of PD1/PDL-1 in the pathogenesis of VL using murine model of VL...
April 2, 2018: Infection and Immunity
https://www.readbyqxmd.com/read/29599411/cd103-tumor-resident-cd8-t-cells-are-associated-with-improved-survival-in-immunotherapy-naive-melanoma-patients-and-expand-significantly-during-anti-pd1-treatment
#18
Jarem Edwards, James S Wilmott, Jason Madore, Tuba N Gide, Camelia Quek, Annie Tasker, Angela L Ferguson, Jinbiao Chen, Rehana Hewavisenti, Peter Hersey, Thomas Gebhardt, Wolfgang Weninger, Warwick J Britton, Robyn Saw, John F Thompson, Alexander M Menzies, Georgina V Long, Richard A Scolyer, Umaimainthan Palendira
PURPOSE: Therapeutic blockade of immune checkpoints has revolutionized cancer treatment. Durable responses however, occur in less than half of those treated and efforts to improve treatment efficacy are confounded by a lack of understanding of the characteristics of the cells that initiate anti-tumor immune response. Experimental Design: We performed multi-parameter flow cytometry and quantitative multiplex immunofluorescence staining on tumor specimens from immunotherapy-naïve melanoma patients and longitudinal biopsy specimen obtained from patients undergoing anti-PD-1 therapy...
March 29, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29593889/immunotherapy-combination-strategies-non-chemotherapy-in-non-small-cell-lung-cancer
#19
REVIEW
Sandrine Niyongere, Andreas Saltos, Jhanelle E Gray
Immune checkpoint inhibitors enhance the activation and antitumor activity of the immune system, resulting in durable response rates in a select group of patients. Cytotoxic T lymphocyte antigen 4 (CTLA4) inhibitors target the inhibitory interaction between CTLA4 and CD80 or CD86. Programmed death 1 (PD1) inhibitors target the interaction between PD1 receptors on T-cells and PD-ligand 1 (PD-L1) and PD-ligand 2, blocking the inhibitory signaling and resulting in activation of T-cell effector function. These therapeutic drugs were originally evaluated in patients with metastatic melanoma before expansion to all tumor types, including non-small cell lung cancer (NSCLC) with promising results...
February 2018: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/29575535/inhibition-of-yes-associated-protein-down-regulates-pd-l1-cd274-expression-in-human-malignant-pleural-mesothelioma
#20
Ping-Chih Hsu, Jinbai Miao, Yu-Cheng Wang, Wen-Qian Zhang, Yi-Lin Yang, Chih-Wei Wang, Cheng-Ta Yang, Zhen Huang, Joanna You, Zhidong Xu, David M Jablons, Liang You
Although tumour PD-L1 (CD274) expression had been used as a predictive biomarker in checkpoint immunotherapy targeting the PD1/PD-L1 axis in various cancers, the regulation of PD-L1 (CD274) expression is unclear. Yes-associated protein (YAP), an important oncogenic protein in Hippo signalling pathway, reportedly promotes cancer development. We investigated whether inhibition of YAP down-regulates PD-L1 (CD274) in human malignant pleural mesothelioma (MPM). Western blotting showed that 2 human MPM cell lines (H2052 and 211H) had increased PD-L1 protein expression compared to H290, MS-1 and H28 cells...
March 24, 2018: Journal of Cellular and Molecular Medicine
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