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https://www.readbyqxmd.com/read/28449473/anti-pd-1-pd-l1-antibody-versus-conventional-chemotherapy-for-previously-treated-advanced-non-small-cell-lung-cancer-a-meta-analysis-of-randomized-controlled-trials
#1
Yongxun Zhuansun, Fengting Huang, Yumo Du, Lin Lin, Rui Chen, Jianguo Li
BACKGROUND: The anti-PD-1/PD-L1 monoclonal antibody has showed promising results in various cancers via enhancing T cell functions. However, many questions remain in the role and safety in previously-treated, advanced non-small-cell lung cancer (NSCLC). Thus, we conducted a meta-analysis incorporating all available evidences to evaluate the efficacy and safety of anti-PD-1/PD-L1 antibody compared with chemotherapy. METHODS: PubMed, Web of Science and the Cochrane Library database were searched for the studies about the efficacy and safety of anti-PD-1/PD-L1 antibody in previously-treated, progressive NSCLC patients...
March 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28447277/assessment-of-pd-1-positive-cells-on-initial-and-secondary-resected-tumor-specimens-of-newly-diagnosed-glioblastoma-and-its-implications-on-patient-outcome
#2
Tsubasa Miyazaki, Eiichi Ishikawa, Masahide Matsuda, Hiroyoshi Akutsu, Satoru Osuka, Noriaki Sakamoto, Shingo Takano, Tetsuya Yamamoto, Koji Tsuboi, Akira Matsumura
Glioblastoma (GBM) is the most common type of malignant brain tumor and has a very poor prognosis. Most patients relapse within 12 months despite aggressive treatment and patient outcome after recurrent is extremely worse. This study was designed to clarify the change of the molecular expression, including programmed cell death 1 (PD-1) and PD-ligand 1 (PD-L1), on the initial and secondary resected tumor specimens and to address the influence of these expressions for patient outcome after second surgery of glioblastoma...
April 26, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28446641/risk-of-pneumonitis-associated-with-programmed-cell-death-1-%C3%A2-inhibitors-in-cancer-patients-a-%C3%A2-meta-analysis
#3
Sheng Zhang, Fei Liang, Ji Zhu, Qiang Chen
Pneumonitis, a rare but potentially life-threatening adverse event in cancer patients receiving programmed death-1 (PD-1) or programmed death ligand-1 (PD-L1) inhibitors, has been reported in case reports, clinical trials and retrospective studies. We performed a systematic review and meta-analysis to calculate the relative risk of pneumonitis associated with the use of PD-1/L1 inhibitors in randomized clinical trials (RCTs).We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, trial registers, conference proceedings, review articles, and reference lists of trial publications for all relevant randomized trials RCTs comparing PD-1/L1 inhibitors to control with available data on pneumonitis...
April 26, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28446544/cellular-expression-of-pd-l1-in-the-peripheral-blood-of-lung-cancer-patients-is-associated-with-worse-survival
#4
Daniel J Boffa, Ryon P Graf, Michelle C Salazar, Jessica Hoag, David Lu, Rachel Krupa, Jessica Louw, Lyndsey Dugan, Yipeng Wang, Mark Landers, Mahipal Suraneni, Stephanie B Greene, Samir Makani, Marisa Magaña, Lyudmila Bazhenova, Ryan V Dittamore, Jorge Nieva
BACKGROUND: Lung cancer treatment has become increasingly dependent upon invasive biopsies to profile tumors for personalized therapy. Recently, tumor expression of PD-L1 has gained interest as a potential predictor of response to immunotherapy. Circulating biomarkers present an opportunity for tumor profiling without the risks of invasive procedures. We characterized PD-L1 expression within populations of nucleated cells in the peripheral blood of lung cancer patients in hopes of expanding the role of liquid biopsy in this setting...
April 26, 2017: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/28446465/deletion-of-lactate-dehydrogenase-a-in-myeloid-cells-triggers-antitumor-immunity
#5
Pankaj Seth, Eva Csizmadia, Andreas Hedblom, Marta Vuerich, Han Xie, Mailin Li, Maria Serena Longhi, Barbara Wegiel
Immunometabolism is emerging as a critical determinant of cancer pathophysiology. In this study, we explored the contributions of macrophage-expressed lactate dehydrogenase-A (LDH-A) to tumor formation in a K-Ras murine model of lung carcinoma. Myeloid-specific deletion of LDH-A promoted accumulation of macrophages with a CD86high and MCP-1high M1-like phenotype that suppressed tumor growth. This phenotypic effect was accompanied by reduced VEGF expression and angiogenesis; diminished numbers of PD-L1+ cancer cells; increased numbers of CD3+ T cells and activation status of CD8+ T cells...
April 26, 2017: Cancer Research
https://www.readbyqxmd.com/read/28445951/pd-l1-expression-in-perihilar-and-intrahepatic-cholangiocarcinoma
#6
Jacqueline Fontugne, Jérémy Augustin, Anaïs Pujals, Philippe Compagnon, Benoit Rousseau, Alain Luciani, Christophe Tournigand, Daniel Cherqui, Daniel Azoulay, Jean-Michel Pawlotsky, Julien Calderaro
Cholangiocarcinoma is an aggressive biliary neoplasm lacking effective therapeutic agents. Immunotherapies targeting the PD-L1/PD-1 immune checkpoint have shown encouraging results in solid and hematologic cancers in clinical trials. Response to these immunomodulators is correlated with PD-L1 expression. Our goal was to characterize PD-L1 expression in intra-hepatic (iCCA) and perihilar (pCCA) cholangiocarcinomas, and to correlate our results with clinicopathological features, density of tumor-infiltrating lymphocytes (TILs) and PD-1 expression...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445479/in-vitro-and-in-vivo-antivirus-activity-of-an-anti-programmed-death-ligand-1-pd-l1-rat-bovine-chimeric-antibody-against-bovine-leukemia-virus-infection
#7
Asami Nishimori, Satoru Konnai, Tomohiro Okagawa, Naoya Maekawa, Ryoyo Ikebuchi, Shinya Goto, Yamato Sajiki, Yasuhiko Suzuki, Junko Kohara, Satoshi Ogasawara, Yukinari Kato, Shiro Murata, Kazuhiko Ohashi
Programmed death-1 (PD-1), an immunoinhibitory receptor on T cells, is known to be involved in immune evasion through its binding to PD-ligand 1 (PD-L1) in many chronic diseases. We previously found that PD-L1 expression was upregulated in cattle infected with bovine leukemia virus (BLV) and that an antibody that blocked the PD-1/PD-L1 interaction reactivated T-cell function in vitro. Therefore, this study assessed its antivirus activities in vivo. First, we inoculated the anti-bovine PD-L1 rat monoclonal antibody 4G12 into a BLV-infected cow...
2017: PloS One
https://www.readbyqxmd.com/read/28444111/pattern-recognition-receptors-immune-targets-to-enhance-cancer-immunotherapy
#8
T Shekarian, S Valsesia-Wittmann, J Brody, M C Michallet, S Depil, C Caux, A Marabelle
Durable tumor responses and significant levels of disease control rates have been described in more than 20 advanced/metastatic cancer types with B7-family immune checkpoint-targeted anti-CTLA-4, anti-PD-1, and anti-PD-L1 monoclonal antibodies. These results and the recent approvals of ipilimumab, pembrolizumab, nivolumab and atezolizumab are currently revolutionizing the way we envision the future of cancer care. However these clinical benefits are not observed in all cancer types and in every patient. Therefore, our clinical challenge is to identify therapeutic strategies which could overcome the primary and secondary resistances to these novel cancer immunotherapies...
April 21, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28442920/a-blockade-of-pd-l1-produced-antitumor-and-antimetastatic-effects-in-an-orthotopic-mouse-pancreatic-cancer-model-via-the-pi3k-akt-mtor-signaling-pathway
#9
Lei Zhao, Cheng Li, Fei Liu, Yonghong Zhao, Jun Liu, Ye Hua, Jinyang Liu, Jiapeng Huang, Chunlin Ge
BACKGROUND: Pancreatic cancer is one of the most aggressive and intractable malignant tumors, and most deaths from pancreatic cancer are related to metastases. It has been demonstrated in vitro that overexpression of programmed death-ligand 1 (PD-L1) correlates with a lack of phosphatase and tensin homologue (PTEN) expression in pancreatic cancer tissue. This loss of PTEN expression may aberrantly activate the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway, and thereby promote tumor cell survival, proliferation, and disease progression...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28442891/spotlight-on-nivolumab-in-the-treatment-of-renal-cell-carcinoma-design-development-and-place-in-therapy
#10
REVIEW
Vyshak Alva Venur, Monika Joshi, Kenneth G Nepple, Yousef Zakharia
Several tyrosine kinase inhibitors targeting the vascular endothelial growth factor receptors and molecules inhibiting the mammalian target of rapamycin are being used for management of metastatic renal cell carcinoma (mRCC); however, there is still a potential for improvement. Immune checkpoint inhibitors like nivolumab and other PD-1/PD-L1 inhibitors provide an alternative approach for patients with mRCC. In this article, the authors review the safety profile and outcomes of phase 1, 2, and 3 clinical trials of nivolumab in mRCC...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28441111/phase-ii-study-of-the-efficacy-and-safety-of-pembrolizumab-for-relapsed-refractory-classic-hodgkin-lymphoma
#11
Robert Chen, Pier Luigi Zinzani, Michelle A Fanale, Philippe Armand, Nathalie A Johnson, Pauline Brice, John Radford, Vincent Ribrag, Daniel Molin, Theodoros P Vassilakopoulos, Akihiro Tomita, Bastian von Tresckow, Margaret A Shipp, Yinghua Zhang, Alejandro D Ricart, Arun Balakumaran, Craig H Moskowitz
Purpose Hodgkin Reed-Sternberg cells harbor alterations in chromosome 9p24.1, leading to overexpression of programmed death-ligand 1 (PD-L1) and PD-L2. Pembrolizumab, a programmed death 1-blocking antibody, demonstrated a high overall response rate (ORR) in patients with relapsed or refractory classic Hodgkin lymphoma (rrHL) in phase I testing. Methods KEYNOTE-087 ( ClinicalTrials.gov identifier, NCT02453594) was a single-arm phase II study of pembrolizumab in three cohorts of patients with rrHL, defined on the basis of lymphoma progression after (1) autologous stem cell transplantation (ASCT) and subsequent brentuximab vedotin (BV); (2) salvage chemotherapy and BV, and thus, ineligible for ASCT because of chemoresistant disease; and (3) ASCT, but without BV after transplantation...
April 25, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28440953/immunotherapy-with-single-agent-nivolumab-for-advanced-leiomyosarcoma-of-the-uterus-results-of-a-phase-2-study
#12
Eytan Ben-Ami, Constance M Barysauskas, Sarah Solomon, Kadija Tahlil, Rita Malley, Melissa Hohos, Kathleen Polson, Margaret Loucks, Mariano Severgnini, Tara Patel, Amy Cunningham, Scott J Rodig, F Stephen Hodi, Jeffrey A Morgan, Priscilla Merriam, Andrew J Wagner, Geoffrey Shapiro, Suzanne George
BACKGROUND: Immunotherapy has changed the therapeutic landscape in oncology. Advanced uterine leiomyosarcoma (ULMS) remains an incurable disease in most cases, and despite new drug approvals, improvements in overall survival have been modest at best. The goal of this study was to evaluate programmed-death 1 (PD-1) inhibition with nivolumab in this patient population. METHODS: This single-center phase 2 trial completed enrollment between May and October 2015. Patients received 3 mg/kg of intravenous nivolumab on day 1 of each 2-week cycle until disease progression or unacceptable toxicity...
April 25, 2017: Cancer
https://www.readbyqxmd.com/read/28439267/pulmonary-delivery-of-virosome-bound-antigen-enhances-antigen-specific-cd4-t-cell-proliferation-compared-to-liposome-bound-or-soluble-antigen
#13
Rebecca A M Blom, Mario Amacker, R Maarten van Dijk, Christian Moser, Philip A Stumbles, Fabian Blank, Christophe von Garnier
Pulmonary administration of biomimetic nanoparticles loaded with antigen may represent an effective strategy to directly modulate adaptive immune responses in the respiratory tract. Depending on the design, virosomes may not only serve as biomimetic antigen carriers but are also endowed with intrinsic immune-stimulatory properties. We designed fluorescently labeled influenza-derived virosomes and liposome controls coupled to the model antigen ovalbumin to investigate uptake, phenotype changes, and antigen processing by antigen-presenting cells exposed to such particles in different respiratory tract compartments...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28438774/avelumab-impresses-in-merkel-cell-carcinoma
#14
(no author information available yet)
The PD-L1 inhibitor avelumab-approved by the FDA in March for the treatment of Merkel cell carcinoma-demonstrated a high number of durable responses in an international, open-label, prospective phase II study. The results of the study, which supported the FDA's decision, were presented in April at the American Association for Cancer Research (AACR) Annual Meeting 2017.
April 24, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28438290/programmed-death-ligand-1-pd-l1-expression-and-tumor-microenvironment-implications-for-patients-with-oral-precancerous-lesions
#15
Takahiro Yagyuu, Kinta Hatakeyama, Mitsuhiko Imada, Miyako Kurihara, Yumiko Matsusue, Kazuhiko Yamamoto, Chiho Obayashi, Tadaaki Kirita
OBJECTIVES: Cancer immunoediting represents a relatively novel concept attempting to explain the process of tumor escape from the host immune system response. Here, we attempted to elucidate the role of programmed death ligand 1 (PD-L1), the tumor microenvironment, and tumor escape mechanisms that allow malignant transformation of oral precancerous lesions. MATERIALS AND METHODS: Patients with oral precancerous lesions managed at the Nara Medical University Hospital, Japan, (n=120) were enrolled in this study...
May 2017: Oral Oncology
https://www.readbyqxmd.com/read/28436319/in-vitro-antioxidant-and-in-vivo-hypolipidemic-effects-of-the-king-oyster-culinary-medicinal-mushroom-pleurotus-eryngii-var-ferulae-ddl01-agaricomycetes-in-rats-with-high-fat-diet-induced-fatty-liver-and-hyperlipidemia
#16
Jun-Hui Choi, Dae-Won Kim, Seung Kim, Sung-Jun Kim
We investigated the effect of the culinary-medicinal mushroom Pleurotus eryngii var. ferulae DDL01 on oxidative damage in the liver and brain and a high-fat/high-cholesterol-induced hyperlipidemic model. In in vitro studies, the water extracts of the fruiting bodies showed strong scavenging activities of DPPH (139.46 ± 3.2 μg) and hydroxyl (139.46 ± 3.2 μg) radicals. Moreover, the extracts showed Fe2+ chelating and reducing abilities, as well as a large amount of polyphenols and an inhibitory effect on lipid peroxidation in the liver and brain tissues...
2017: International Journal of Medicinal Mushrooms
https://www.readbyqxmd.com/read/28435290/altered-status-of-programmed-death-ligand-1-after-recurrence-in-resected-lung-adenocarcinoma-patients
#17
Jun Chen, Hui Li, Ronglin Pang, Jia Huang
PURPOSE: Programmed death-ligand 1 (PD-L1) is found to be overexpressed in non-small cell lung cancer. The present study intended to evaluate the status of PD-L1 expression in patients with resection and recurrent lung adenocarcinoma. PATIENTS AND METHODS: Matched resection and recurrent tumor samples were harvested from 65 lung adenocarcinoma patients. Immunohistochemistry was used to evaluate the status of PD-L1 expression. Kaplan-Meier method was used for survival analysis...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28434510/pd-l1-testing-for-immune-checkpoint-inhibitors-in-mesothelioma-for-want-of-anything-better
#18
EDITORIAL
Sylvie Lantuejoul, Nolwenn Le Stang, Francesca Damiola, Arnaud Scherpereel, Francoise Galateau-Sallé
No abstract text is available yet for this article.
May 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28434399/the-next-generation-of-immunotherapy-keeping-lung-cancer-in-check
#19
REVIEW
Ashwin Somasundaram, Timothy F Burns
Lung cancer is the deadliest malignancy with more cancer deaths per year than the next three cancers combined. Despite remarkable advances in targeted therapy, advanced lung cancer patients have not experienced a significant improvement in mortality. Lung cancer has been shown to be immunogenic and responsive to checkpoint blockade therapy. Checkpoint signals such as CTLA-4 and PD-1/PD-L1 dampen T cell activation and allow tumors to escape the adaptive immune response. Response rates in patients with pretreated, advanced NSCLC were much higher and more durable with PD-1 blockade therapy compared to standard-of-care, cytotoxic chemotherapy...
April 24, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28434031/fkbp51s-signature-in-peripheral-blood-mononuclear-cells-of-melanoma-patients-as-a-possible-predictive-factor-for-immunotherapy
#20
Simona Romano, Ester Simeone, Anna D'Angelillo, Paolo D'Arrigo, Michele Russo, Mario Capasso, Vito Alessandro Lasorsa, Nicola Zambrano, Paolo A Ascierto, Maria Fiammetta Romano
The inhibitory immune checkpoint PD-L1/PD1 promotes the alternative splicing of the FKBP5 gene, resulting in increased expression of its variant 4 in the peripheral blood mononuclear cells of melanoma patients. The variant 4 transcript is translated into the truncated FKBP51s protein. Given the importance of co-inhibitory signalling in tumour immune escape, here we tested the potential for using FKBP51s expression to predict immunotherapy outcomes. To do this, we immunophenotyped PBMCs from 118 melanoma patients and 77 age- and sex-matched healthy controls...
April 22, 2017: Cancer Immunology, Immunotherapy: CII
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