Read by QxMD icon Read


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
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
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
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
San-Chi Chen, Peter Mu-Hsin Chang, Hsiao-Jung Wang, Shyh-Kuan Tai, Pen-Yuan Chu, Muh-Hwa Yang
PD-L1 expression is critical in helping tumor cells evade the immune system. However, the level of PD-L1 expression in non-oropharyngeal head and neck squamous cell carcinoma (non-OPHNSCC) and its association with patient prognosis remains unclear. A retrospective clinicopathological analysis was performed on 106 patients with non-OPHNSCC diagnosed between 2007 and 2014. In the current study, tissue arrays from paraffin-embedded non-OPHNSCC samples obtained from patients were constructed, and PD-L1 and p16 INK4A expression were determined using immunohistochemistry...
February 2018: Oncology Letters
Salvatore Alfieri, Stefano Cavalieri, Lisa Licitra
PURPOSE OF REVIEW: In the last decade, after cetuximab (anti-epidermal growth factor receptor), none of the novel investigated compounds has demonstrated benefit in head and neck squamous cell cancers (HNSCC), both in advanced and curative settings. Therefore, prognosis of recurrent/metastatic (R/M) HNSCC patients remains dismal, especially in platinum-refractory cohort. In the last few years, a new important class of drugs has affirmed its role. HNSCC, even if less 'immunogenic' than other malignancies (e...
April 2018: Current Opinion in Otolaryngology & Head and Neck Surgery
Bhagyashree Bhagwat, Holly Cherwinski, Manjiri Sathe, Wolfgang Seghezzi, Terrill K McClanahan, Rene de Waal Malefyt, Aarron Willingham
LAG3 is an important regulator of T cell homeostasis and studies in mouse tumor models have demonstrated that simultaneously antagonizing LAG3 and PD1 can augment tumor-specific T cell responses and induce tumor rejection. The combined use of LAG3 antagonist antibodies with established anti-PD1 therapies is currently being evaluated in human clinical trials. A functional assay for human LAG3 was developed by co-culture of a Jurkat T-cell lymphoma line overexpressing LAG3 with a Raji B-cell lymphoma line in the presence of staphylococcal enterotoxins...
February 7, 2018: Journal of Immunological Methods
Paul Zolkind, Dariusz Przybylski, Nemanja Marjanovic, Lan Nguyen, Tianxiang Lin, Tanner Johanns, Anton Alexandrov, Liye Zhou, Clint T Allen, Alexander P Miceli, Robert D Schreiber, Maxim Artyomov, Gavin P Dunn, Ravindra Uppaluri
Head and neck squamous cell carcinomas (HNSCC) are an ideal immunotherapy target due to their high mutation burden and frequent infiltration with lymphocytes. Preclinical models to investigate targeted and combination therapies as well as defining biomarkers to guide treatment represent an important need in the field. Immunogenomics approaches have illuminated the role of mutation-derived tumor neoantigens as potential biomarkers of response to checkpoint blockade as well as representing therapeutic vaccines...
January 9, 2018: Oncotarget
Florian S Dreyer, Martina Cantone, Martin Eberhardt, Tanushree Jaitly, Lisa Walter, Jürgen Wittmann, Shailendra Gupta, Faiz Khan, Olaf Wolkenhauer, Brigitte Pützer, Hans-Martin Jäck, Lucie Heinzerling, Julio Vera
Cellular phenotypes are established and controlled by complex and precisely orchestrated molecular networks. In cancer, mutations and dysregulations of multiple molecular factors perturb the regulation of these networks and lead to malignant transformation. High-throughput technologies are a valuable source of information to establish the complex molecular relationships behind the emergence of malignancy, but full exploitation of this massive amount of data requires bioinformatics tools that rely on network-based analysis...
February 2, 2018: Biochimica et Biophysica Acta
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"