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Anti pd1

Alessio Cortellini, Melissa Bersanelli, Sebastiano Buti, Elisabetta Gambale, Francesco Atzori, Federica Zoratto, Alessandro Parisi, Davide Brocco, Annagrazia Pireddu, Katia Cannita, Daniela Iacono, Maria R Migliorino, Teresa Gamucci, Michele De Tursi, Tina Sidoni, Maria Tiseo, Maria Michiara, Anselmo Papa, Gesuino Angius, Silverio Tomao, Maria C Fargnoli, Clara Natoli, Corrado Ficorella
AIM: Tumors related to hereditary susceptibility seem to have an immunosensitive phenotype. MATERIALS & METHODS: We conducted a multicenter retrospective study, to investigate if family history of cancer, multiple neoplasms and early onset of cancer could be related to clinical outcomes of anti-PD-1/PD-L1 therapy. Activity and efficacy data of 211 advanced cancer patients (kidney, non-small-cell lung cancer, melanoma, urothelium, colorectal and HeN), treated at seven Italian centers with anti-PD-1/PD-L1 agents, were analyzed...
March 22, 2018: Immunotherapy
Anne Mills, Sara Zadeh, Emily Sloan, Zachary Chinn, Susan C Modesitt, Kari L Ring
Mismatch repair-deficient endometrial carcinomas are optimal candidates for immunotherapy given their high neoantigen loads, robust lymphoid infiltrates, and frequent PD-L1 expression. However, co-opting the PD-1/PD-L1 pathway is just one mechanism that tumors can utilize to evade host immunity. Another immune modulatory molecule that has been demonstrated in endometrial carcinoma is indoleamine 2,3-dioxygenase (IDO). We herein evaluate IDO expression in 60 endometrial carcinomas and assess results in relation to PD-L1 and mismatch repair status...
March 20, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Nicolas Gourdin, Marion Bossennec, Céline Rodriguez, Selena Vigano, Christelle Machon, Camilla Jandus, David Bauché, Julien Faget, Isabelle Durand, Nicolas Chopin, Olivier Tredan, Julien C Marie, Bertrand Dubois, Jérôme Guitton, Pedro Romero, Christophe Caux, Christine Ménétrier-Caux
The production of CD73-derived Adenosine (Ado) by Tregs, has been proposed as a resistance mechanism to anti-PD1 therapy in murine tumor models. We reported that Human Tregs express the ecto-nucleotidase CD39, that generates AMP from ATP, but do not express the AMPase CD73. In contrast, CD73 defined a subset of effector CD4+ T cells (Teffs), enriched in polyfunctional Th1.17 cells characterized by expression of CXCR3, CCR6 and MDR1 and production of IL-17A/IFN-γ/IL-22/GM-CSF. CD39+ Tregs selectively targeted CD73+ Teffs through cooperative degradation of ATP into Ado inhibiting and restricting the ability of CD73+ Teffs to secrete IL-17A...
March 20, 2018: Cancer Research
Benjamin Benzon, Stephanie A Glavaris, Brian W Simons, Robert M Hughes, Kamyar Ghabili, Patrick Mullane, Rebecca Miller, Katriana Nugent, Brian Shinder, Jeffrey Tosoian, Ephraim J Fuchs, Phuoc T Tran, Paula J Hurley, Milena Vuica-Ross, Edward M Schaeffer, Charles G Drake, Ashley E Ross
BACKGROUND: Prostate cancer remains the second leading cause of cancer related death in men. Immune check point blocking antibodies have revolutionized treatment of multiple solid tumors, but results in prostate cancer remain marginal. Previous reports have suggested that local therapies, in particular cryoablation might increase tumor immunogenicity. In this work, we examine potential synergism between tumor cryoabalation and check point blocking antibodies. METHODS: FVB/NJ mice were injected subcutaneously into each flank with either 1 × 106 or 0...
March 20, 2018: Prostate Cancer and Prostatic Diseases
Margaux Garnier, Julia Zaragoza, Nathalie Bénéton, Guido Bens, Victoire Meurisse, Mahtab Samimi, Hervé Maillard, Laurent Machet
No abstract text is available yet for this article.
March 12, 2018: Journal of the American Academy of Dermatology
James L Quinn, Gaurav Kumar, Agnieshka Agasing, Rose M Ko, Robert C Axtell
Both T cells and B cells are implicated in the pathology of multiple sclerosis (MS), but how these cells cooperate to drive disease remains unclear. Recent studies using experimental autoimmune encephalomyelitis (EAE) demonstrated that the TH17 pathway is correlated with increased numbers of ectopic B-cell follicles in the central nervous system (CNS). As follicular T helper (TFH) cells are regulators of B cell responses, we sought to examine the role of TFH cells in EAE induced by the transfer of myelin-specific TH17 cells (TH17-EAE)...
2018: Frontiers in Immunology
Xuanwei Zhang, Gabriele Niedermann
PURPOSE: Hypofractionated radiation therapy (hRT) combined with immune checkpoint blockade can induce T-cell-mediated local and abscopal antitumor effects. We had previously observed peak levels of tumor-infiltrating lymphocytes (TILs) between days 5 and 8 after hRT. Because TILs are regarded as radiosensitive, hRT schedules extending into this period might be less immunogenic, prompting us to compare clinically relevant, short and extended schedules with equivalent biologically effective doses combined with anti-programmed cell death 1 (PD1) antibody treatment...
February 3, 2018: International Journal of Radiation Oncology, Biology, Physics
Franz L Ricklefs, Quazim Alayo, Harald Krenzlin, Ahmad B Mahmoud, Maria C Speranza, Hiroshi Nakashima, Josie L Hayes, Kyungheon Lee, Leonora Balaj, Carmela Passaro, Arun K Rooj, Susanne Krasemann, Bob S Carter, Clark C Chen, Tyler Steed, Jeffrey Treiber, Scott Rodig, Katherine Yang, Ichiro Nakano, Hakho Lee, Ralph Weissleder, Xandra O Breakefield, Jakub Godlewski, Manfred Westphal, Katrin Lamszus, Gordon J Freeman, Agnieszka Bronisz, Sean E Lawler, E Antonio Chiocca
Binding of programmed death ligand-1 (PD-L1) to programmed cell death protein-1 (PD1) leads to cancer immune evasion via inhibition of T cell function. One of the defining characteristics of glioblastoma, a universally fatal brain cancer, is its profound local and systemic immunosuppression. Glioblastoma has also been shown to generate extracellular vesicles (EVs), which may play an important role in tumor progression. We thus hypothesized that glioblastoma EVs may be important mediators of immunosuppression and that PD-L1 could play a role...
March 2018: Science Advances
Maria Rita Gaiser, Nikolas von Bubnoff, Christoffer Gebhardt, Jochen Sven Utikal
During the last six years, several innovative, systemic therapies for the treatment of metastatic malignant melanoma (MM) have emerged. Conventional chemotherapy has been superseded by novel first-line therapies, including systemic immunotherapies (anti-CTLA4 and anti-PD1; authorization of anti-PDL1 is anticipated) and therapies targeting specific mutations (BRAF, NRAS, and c-KIT). Thus, treating physicians are confronted with new challenges, such as stratifying patients for appropriate treatments and monitoring long-term responders for progression...
March 7, 2018: Journal der Deutschen Dermatologischen Gesellschaft, Journal of the German Society of Dermatology: JDDG
Jessica Moskovitz, Jennifer Moy, Robert L Ferris
PURPOSE OF REVIEW: Discussion of current strategies targeting the immune system related to solid tumors with emphasis on head and neck squamous cell carcinoma (HNSCC).This review will outline the current challenges with immunotherapy and future goals for treatment using these agents. RECENT FINDINGS: Agents targeting immune checkpoint receptors (IR) such as program death 1 (PD1) have been used in the clinical realm for melanoma and non-small cell lung cancer (NSCLC), and the use of these agents for these malignancies has provided crucial information about how and why patients respond or not to inhibitory checkpoint receptor blockade therapy (ICR)...
March 3, 2018: Current Oncology Reports
Jakob Nikolas Kather, Niels Halama, Dirk Jaeger
Colorectal cancer (CRC) is a common and lethal disease with a high therapeutic need. For most patients with metastatic CRC, chemotherapy is the only viable option. Currently, immunotherapy is restricted to the particular genetic subgroup of mismatch-repair deficient (MMRd)/microsatellite instable (MSI) CRC. Anti-PD1 therapy was recently FDA-approved as a second-line treatment in this subgroup. However, in a metastatic setting, these MMRd/MSI tumors are vastly outnumbered by mismatch-repair proficient (MMRp)/microsatellite stable (MSS) tumors...
March 1, 2018: Seminars in Cancer Biology
Erik Ladomersky, Lijie Zhai, Alicia Lenzen, Kristen L Lauing, Jun Qian, Denise M Scholtens, Galina Gritsina, Xuebing Sun, Ye Liu, Fenglong Yu, Wenfeng Gong, Yong Liu, Beibei Jiang, Zhiyu Tang, Ricky Patel, Leonidas C Platanias, C David James, Roger Stupp, Rimas V Lukas, David C Binder, Derek A Wainwright
PURPOSE: Glioblastoma (GBM) is the most aggressive primary brain tumor in adults with a median survival of 15-20 months. Numerous approaches and novel therapeutics for treating GBM have been investigated in the setting of phase III clinical trials, including a recent analysis of the immune checkpoint inhibitor, Nivolumab (anti-PD-1), which failed to improve recurrent GBM patient survival. However, rather than abandoning immune checkpoint inhibitor treatment for GBM, which has shown promise in other types of cancer, ongoing studies are currently evaluating this therapeutic class when combined with other agents...
March 2, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Paul J Bröckelmann, Stephanie Sasse, Andreas Engert
With defined chemo- and radiotherapy and risk-adapted treatment, early-stage classical Hodgkin lymphoma (HL) has become curable in the majority of patients. A major current goal is hence to reduce treatment-related toxicity while maintaining long-term disease control. Patients with early-stage favorable disease, i.e. limited stage without risk factors (RFs), are frequently treated with two cycles of doxorubicin, bleomycin, vinblastine and dacarbazine (2xABVD) followed by 20Gy involved-field or -site radiotherapy (IF/IS-RT)...
March 2, 2018: Blood
Alberto Carretero-González, David Lora, Ismael Ghanem, Jon Zugazagoitia, Daniel Castellano, Juan M Sepúlveda, José A López-Martin, Luis Paz-Ares, Guillermo de Velasco
Background: Anti-PD1/PD-L1 monoclonal antibodies (mAbs) increase overall survival compared to standard of care (SOC) in different tumors. However, a proportion of patients (pts) will have progressive disease (PD) as best response. We conducted a meta-analysis to study the rates of response comparing these antibodies with SOC. Methods: A search of published trials in MEDLINE and EMBASE analyzing anti-PD1/PD-L1mAbs monotherapy compared to SOC. Relative risk (RR) with 95% confidence interval (CI) of response rates between groups was estimated...
February 2, 2018: Oncotarget
Yanxia Guo, Alice M Walsh, Mary Canavan, Mihir D Wechalekar, Suzanne Cole, Xuefeng Yin, Brittney Scott, Mathew Loza, Carl Orr, Trudy McGarry, Michele Bombardieri, Frances Humby, Susanna M Proudman, Costantino Pitzalis, Malcolm D Smith, Joshua R Friedman, Ian Anderson, Loui Madakamutil, Douglas J Veale, Ursula Fearon, Sunil Nagpal
Immune checkpoint blockade with therapeutic anti-cytotoxic T lymphocyte-associated antigen (CTLA)-4 (Ipilimumab) and anti-programmed death (PD)-1 (Nivolumab and Pembrolizumab) antibodies alone or in combination has shown remarkable efficacy in multiple cancer types, concomitant with immune-related adverse events, including arthralgia and inflammatory arthritis (IA) in some patients. Herein, using Nivolumab (anti-PD-1 antagonist)-responsive genes along with transcriptomics of synovial tissue from multiple stages of rheumatoid arthritis (RA) disease progression, we have interrogated the activity status of PD-1 pathway during RA development...
2018: PloS One
Jooeun Bae, Teru Hideshima, Yu-Tzu Tai, Yan Song, Paul Richardson, Noopur Raje, Nikhil C Munshi, Kenneth C Anderson
Histone deacetylases (HDAC) are therapeutic targets in multiple cancers. ACY241, an HDAC6 selective inhibitor, has shown anti-multiple myeloma (MM) activity in combination with immunomodulatory drugs and proteasome inhibitors. Here we show ACY241 significantly reduces the frequency of CD138+ MM cells, CD4+ CD25+ FoxP3+ regulatory T cells, and HLA-DRLow/- CD11b+ CD33+ myeloid-derived suppressor cells; and decreases expression of PD1/PD-L1 on CD8+ T cells and of immune checkpoints in bone marrow cells from myeloma patients...
February 22, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Quentin Magis, Caroline Gaudy-Marqueste, Agnes Basire, Anderson Loundou, Nausicaa Malissen, Laura Troin, Sandrine Monestier, Stéphanie Mallet, Sylvie Hesse, Marie-Aleth Richard, René Valéro, Sophie Beliard, Jean-Jacques Grob
Acute type 1 diabetes (AD1) is a rare but definitive immune-related adverse event associated with anti-PD1. Most of the reported cases are close to what has been described as "fulminant type 1 diabetes." We sought to determine whether anti-PD1 could impair glycoregulation and whether occurrence of AD1 could be anticipated by prior glycemic changes. Fasting glycemia collected before, under, and after treatment in melanoma patients treated with anti-PD1 over a period of 36 months were retrospectively analyzed...
February 23, 2018: Journal of Immunotherapy
Arnaud Jannin, Emilie Merlen, Christine Do Cao, Nicolas Penel
Recently developed immunotherapeutic agents, like anti-cytotoxic T lymphocyte antigen 4 antibody (CTLA4), anti-programmed cell death 1 (PD1) or anti-programmed cell death-ligand 1 (PDL1), have demonstrated substantial potential for the treatment of a variety of malignancies. Autoimmune side effects from these agents are diverse and can include multiple endocrinopathies like immunotherapy induced hypophysitis (IH). These toxicities appear to be more frequent in patients receiving anti-CTLA4 antibody compared to PD1/PDL1 agents...
February 20, 2018: Bulletin du Cancer
Manish R Patel
Immune therapy has now been incorporated into the standard of care for non-small-cell lung cancer based on randomized trials showing superiority of anti-PD1 antibodies compared with chemotherapy. Thus there is a renewed interest in immune approaches to treating lung cancer. One promising approach is with oncolytic viruses that either naturally or through engineering, preferentially infect or kill cancer cells. In preclinical models of different thoracic cancers, it has been found that these viruses can induce immune responses through multiple mechanisms...
April 2018: Immunotherapy
Marta Elosua-González, Ana Pampín-Franco, Ramón Mazzucchelli-Esteban, Xabier Mielgo-Rubio, Ximena Rodriguez-Vásquez, Elena García-Zamora, Jose Luis López-Estebaranz
Nivolumab, a monoclonal antibody against the programmed cell death protein 1 (PD-1), has shown promising results in patients with advanced malignancies, including melanoma, lung cancer, and renal cancer. Immune-related adverse events (irAEs) have been reported, including both organ-specific toxicities and skin toxicities. Herein, we report a case of predominantly palmoplantar psoriasis with severe nail involvement, psoriatic arthritis, and autoimmune hypothyroidism after receiving nivolumab treatment for lung cancer...
August 15, 2017: Dermatology Online Journal
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