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PD1 cancer

Liqing Wang, Suresh Kumar, Satinder Dahiya, Feng Wang, Jian Wu, Kheng Newick, Rongxiang Han, Arabinda Samanta, Ulf H Beier, Tatiana Akimova, Tricia R Bhatti, Benjamin Nicholson, Mathew P Kodrasov, Saket Agarwal, David E Sterner, Wei Gu, Joseph Weinstock, Tauseef R Butt, Steven M Albelda, Wayne W Hancock
Foxp3+ T-regulatory (Treg) cells are known to suppress protective host immune responses to a wide variety of solid tumors, but their therapeutic targeting is largely restricted to their transient depletion or "secondary" modulation, e.g. using anti-CTLA-4 monoclonal antibody. Our ongoing studies of the post-translational modifications that regulate Foxp3 demonstrated that the histone/protein acetyltransferase, Tip60, plays a dominant role in promoting acetylation, dimerization and function in Treg cells. We now show that the ubiquitin-specific protease, Usp7, controls Treg function largely by stabilizing the expression and promoting the multimerization of Tip60 and Foxp3...
October 15, 2016: EBioMedicine
J Chee, B W S R Robinson, R A Holt, J Creaney
Harnessing the immune system to fight cancer is an exciting advancement in lung cancer therapy. Anti-tumor immunity can be augmented by checkpoint blockade therapy, which removes the inhibition/brakes imposed on the immune system by the tumor. Checkpoint blockade therapy with anti-PD1/anti-PDL1 antibodies causes tumor regression in around 25% of lung cancer patients. In another approach, the immune system is forced or accelerated to attack the tumour, via augmentation of the anti-tumour response against mutations carried by each lung tumour...
October 18, 2016: Chest
Florian Rouaud, Jean-Luc Boucher, Anny Slama-Schwok, Stéphane Rocchi
Melanoma is one of the most lethal cancers when it reaches a metastatic stage. Despite the spectacular achievements of targeted therapies (BRAF inhibitors) or immuno-therapies (anti-CTLA4 or anti-PD1), most patients with melanoma will need additional treatments. Here we used a photoactive NADPH analogue called NS1 to induce cell death by inhibition of NADPH oxidases NOX in melanoma cells, including melanoma cells isolated from patients. In contrast, healthy melanocytes growth was unaffected by NS1 treatment...
October 14, 2016: Oncotarget
Yi Zheng, Yicheng Yang, Shu Wu, Yongqiang Zhu, Xiaolong Tang, Xiaopeng Liu
As the second most common gynecologic malignant tumors with a high mortality rate, cervical cancer jeopardizes women's life worldwide. The low cure rate in cervical cancer patients is mainly attributed to the lack of effective therapies. One feasible novel strategy is to develop immune-based approaches such as adoptive cell immunotherapy of DCCIKs which represents a promising nontoxic antineoplastic immunotherapy preferred in clinic practice. However, the therapeutic effect is not as efficient as anticipated...
October 18, 2016: Bioengineered
Jung-Jyh Hung, Shiu-Feng Huang, Ying-Ying Shen, Yu-Chung Wu, Teh-Ying Chou, Wen-Hu Hsu
BACKGROUND: The programmed cell death-ligand 1 (PD-L1) pathway plays an important role in maintaining immune homeostasis. The PD-L1 pathway may also protect tumors from attack by cytotoxic T cells. Blockade of programmed cell death 1 (PD1) or PD-L1 induced durable tumor regression in patients with advanced cancers, including non-small cell lung cancer (NSCLC). However, the prognostic value of PD-L1 expression in patients with lung adenocarcinoma remains controversial. METHODS: A total of 112 patients with resected lung adenocarcinoma were included in the study...
October 12, 2016: Annals of Thoracic Surgery
Umberto Maggiore, Julio Pascual
Cancer immunotherapy, especially the use of checkpoint inhibitors, is expanding and can be efficacious in organ transplant recipients with malignant neoplasia. In this review, we summarize clinical findings and evolution of several patients treated with CTL4-4 or PD-1 inhibitors reported in the literature. The CTL-4 inhibitor ipilimumab has been safely used in several liver and kidney allograft recipients. PD1-inhibitors look promising for tumor shrinking, but acute rejection is the rule, so they should be avoided in recipients of life-saving organs...
September 2016: Advances in Chronic Kidney Disease
Jéssica Ribeiro Gomes, Rafael A Schmerling, Carolina K Haddad, Douglas J Racy, Robson Ferrigno, Erlon Gil, Pedro Zanuncio, Antônio C Buzaid
Abscopal effect is a rare phenomenon characterized by tumor regression of untreated metastatic lesions after a local therapy (eg, radiotherapy). We studied the probability of abscopal effect with radiotherapy associated with anti-programmed death cell 1 (PD1) therapy after progression on anti-PD1. This study is a retrospective analysis of patients treated with nivolumab or pembrolizumab for melanoma, non-small cell lung cancer (NSCLC) and renal cancer at Antônio Ermírio de Moraes Oncology Center, Brazil. To be eligible for this analysis, patients must have had unequivocal evidence of disease progression on anti-PD1 therapy and subsequent radiotherapy for any tumor site while still receiving anti-PD1...
November 2016: Journal of Immunotherapy
Julie Bonigen, Christine Raynaud-Donzel, José Hureaux, Nora Kramkimel, Astrid Blom, Géraldine Jeudy, Anne-Laure Breton, Thomas Hubiche, Christophe Bedane, Delphine Legoupil, Anne Pham-Ledard, Julie Charles, Maurice Pérol, Emilie Gérard, Patrick Combemale, Daphné Bonnet, Michèle-Léa Sigal, Emmanuel Mahé
Nivolumab (Opdivo(®) ), pembrolizumab (Keytruda(®) ), atezolizumab, and pidilizumabab are anti-PD1 monoclonal antibodies. Nivolumab is licensed in advanced melanoma and second-line therapy of advanced or metastatic non-small cell lung cancer. When activated, the programmed cell death (PD)-1 is implicated in the inhibition of the immune system. Anti-PD1 removes this inhibition and allows the immune system to control tumour cell progression.(1-4) Immune-mediated toxicity of this treatment have been reported, either organ-specific toxicities - i...
October 14, 2016: Journal of the European Academy of Dermatology and Venereology: JEADV
Paulina Własiuk, Maciej Putowski, Krzysztof Giannopoulos
The appropriate function of the immune system depends on the effective regulation of the immune response on multiple levels. The key element of an effective immune response to antigenic stimulation is maintaining a homeostasis between activation and inhibitory function of immunocompetent cells and molecules. In pathological conditions such as chronic infections, autoimmune diseases or cancer there are significant alterations, and prevalence of signals of one type over another. Main markers of these dysfunctions are altered expressions of molecules, such as programmed death-1 (PD-1), Human Leukocyte Antigen G (HLA-G), or changed percentages of T regulatory cells (Treg)...
October 4, 2016: Postȩpy Higieny i Medycyny Doświadczalnej
C Baues, R Semrau, U S Gaipl, P J Bröckelmann, J Rosenbrock, A Engert, S Marnitz
BACKGROUND: Patients with classical Hodgkin's lymphoma (cHL) have a good prognosis even in advanced stages. However, combined chemo- and radiotherapy, as the standard of care, is also associated with treatment-related toxicities such as organ damage, secondary neoplasias, infertility, or fatigue and long-term fatigue. Many patients suffer from this burden although their cHL was cured. Therefore, the efficacy of immune checkpoint inhibitors like anti-PD1/PD-L1 antibodies in the treatment of solid cancers and also in HL offers new options...
October 4, 2016: Strahlentherapie und Onkologie: Organ der Deutschen Röntgengesellschaft ... [et Al]
Claudio Agostinelli, Andrea Gallamini, Luisa Stracqualursi, Patrizia Agati, Claudio Tripodo, Fabio Fuligni, Maria Teresa Sista, Stefano Fanti, Alberto Biggi, Umberto Vitolo, Luigi Rigacci, Francesco Merli, Caterina Patti, Alessandra Romano, Alessandro Levis, Livio Trentin, Caterina Stelitano, Anna Borra, Pier Paolo Piccaluga, Stephen Hamilton-Dutoit, Peter Kamper, Jan Maciej Zaucha, Bogdan Małkowski, Waldemar Kulikowski, Joanna Tajer, Edyta Subocz, Justyna Rybka, Christian Steidl, Alessandro Broccoli, Lisa Argnani, Randy D Gascoyne, Francesco d'Amore, Pier Luigi Zinzani, Stefano A Pileri
BACKGROUND: Early-interim fluorodeoxyglucose (FDG)-PET scan after two ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy courses (PET-2) represents the most effective predictor of treatment outcome in classical Hodgkin's lymphoma. We aimed to assess the predictive value of PET-2 combined with tissue biomarkers in neoplastic and microenvironmental cells for this disease. METHODS: We enrolled 208 patients with classical Hodgkin's lymphoma and treated with ABVD (training set), from Jan 1, 2002, to Dec 31, 2009, and validated the results in a fully matched independent cohort of 102 patients with classical Hodgkin's lymphoma (validation set), enrolled from Jan 1, 2008, to Dec 31, 2012...
October 2016: Lancet Haematology
Eduardo Castañón
Anti-PD1 antibodies have led to a therapeutic shift in cancer treatment. Although classically described as "well-tolerated", these drugs can lead to severe immune related adverse events. Using CT scan imaging, Nishino and colleagues describe different radiological patterns and their possible relation to severity of several cases of anti-PD1 induced pneumonitis.
September 28, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Barbara Gitlitz, Bonnie Addario, Alicia Sable-Hunt, Silvia Novello, Tiziana Vavala, Ruthia Chen, Marisa Bittoni, S Lani Park, Mark Jennings, Geoffrey Oxnard
No abstract text is available yet for this article.
October 2016: Journal of Thoracic Oncology
Barbara Gitlitz, Bonnie Addario, Alicia Sable-Hunt, Silvia Novello, Tiziana Vavala, Ruthia Chen, Marisa Bittoni, S Lani Park, Mark Jennings, Geoffrey Oxnard
No abstract text is available yet for this article.
October 2016: Journal of Thoracic Oncology
Ralph E Parchment, Andrea Regier Voth, James H Doroshow, Jay A Berzofsky
Immunotherapy has become a major modality of cancer treatment, with multiple new classes of immunotherapeutics recently entering the clinic and obtaining market approval from regulatory agencies. While the promise of these therapies is great, so is the number of possible combinations not only with each other but also with small molecule therapeutics. Furthermore, the observation of unusual dose-response relationships suggests a critical dependency of drug effectiveness on the dosage regimen (dose and schedule)...
August 2016: Seminars in Oncology
Fei Yan, Jiuxia Pang, Yong Peng, Julian R Molina, Ping Yang, Shujun Liu
Although small cell lung cancer (SCLC) is highly responsive to chemotherapies (e.g., cisplatin-etoposide doublet), virtually almost all responsive SCLC patients experience disease recurrence characterized by drug resistance. The mechanisms underlying cisplatin resistance remain elusive. Here we report that cell-intrinsic expression of PD1 and PD-L1, two immune checkpoints, is required for sustained expansion of SCLC cells under cisplatin selection. Indeed, PD1 and PD-L1 were expressed at a higher level in lung cancer cell lines, tumor tissues, and importantly, in SCLC cells resistant to cisplatin (H69R, H82R), when compared to respective controls...
2016: PloS One
Satoru Senju
Antibody-based anti-cancer immunotherapy was recently recognized as one of the truly effective therapies for cancer patients. Antibodies against cell surface cancer antigens, such as CD20, and also those against immune-inhibitory molecules called "immune checkpoint blockers", such as CTLA4 or PD1, have emerged. Large-scale clinical trials have confirmed that, in some cases, antibody-based drugs are superior to conventional chemotherapeutic agents. These antibody-based drugs are now being manufactured employing a mass-production system by pharmaceutical companies...
August 2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Yanqi Ye, Jinqiang Wang, Quanyin Hu, Gabrielle M Hochu, Hongliang Xin, Chao Wang, Zhen Gu
Despite the promising efficacy of immunoregulation in cancer therapy, the clinical benefit has been restricted by inefficient infiltration of lymphocytes in the evolution of immune evasion. Also, immune-related adverse events have often occurred due to the off-target binding of therapeutics to normal tissues after systematic treatment. In light of this, we have developed a synergistic immunotherapy strategy that locally targets the immunoinhibitory receptor programmed cell death protein 1 (PD1) and immunosuppressive enzyme indoleamine 2,3-dioxygenase (IDO) for the treatment of melanoma through a microneedle-based transcutaneous delivery approach...
September 27, 2016: ACS Nano
Brandon S Sheffield, Regan Fulton, Steve E Kalloger, Katy Milne, Georgia Geller, Martin Jones, Celine Jacquemont, Susanna Zachara, Eric Zhao, Erin Pleasance, Janessa Laskin, Steven J M Jones, Marco A Marra, Stephen Yip, Brad H Nelson, Allen M Gown, Cheryl Ho, Diana N Ionescu
Inhibitors of the programmed cell death 1 (PD-1) signaling axis have recently demonstrated efficacy and are rapidly being incorporated into the treatment of non-small cell lung cancers (NSCLCs). Despite clear benefits to certain patients, the association of these responses with a predictive biomarker remains uncertain. Several different biomarkers have been proposed, with differing results and conclusions. This study compares multiple methods of biomarker testing for treatment of NSCLCs with PD1-axis inhibitors...
October 2016: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
David J Birnbaum, Pascal Finetti, Alexia Lopresti, Marine Gilabert, Flora Poizat, Olivier Turrini, Jean-Luc Raoul, Jean-Robert Delpero, Vincent Moutardier, Daniel Birnbaum, Emilie Mamessier, François Bertucci
Pancreatic cancer is one of the most aggressive human cancers. PD1/PDL1-inhibitors recently showed promising results in different cancers with correlation between PDL1 tumor expression and responses. Expression of programmed cell death receptor ligand 1 (PDL1) has been scarcely studied in pancreatic cancer. In this retrospective study, we analyzed PDL1 mRNA expression in 453 clinical pancreatic cancer samples profiled using DNA microarrays and RNASeq. Compared to normal pancreatic samples, PDL1 expression was upregulated in 19% of cancer samples...
August 29, 2016: Oncotarget
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