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F Chen, Y Zhang, E Parra, J Rodriguez, C Behrens, R Akbani, Y Lu, J M Kurie, D L Gibbons, G B Mills, I I Wistuba, C J Creighton
Non-small-cell lung cancer (NSCLC) demonstrates remarkable molecular diversity. With the completion of The Cancer Genome Atlas (TCGA), there is opportunity for systematic analyses of the entire TCGA NSCLC cohort, including comparisons and contrasts between different disease subsets. On the basis of multidimensional and comprehensive molecular characterization (including DNA methylation and copy, and RNA and protein expression), 1023 NSCLC cases-519 from TCGA adenocarcinoma (AD) project and 504 from TCGA squamous cell carcinoma (SQCC) project-were classified using a 'cluster-of-clusters' analytic approach...
October 24, 2016: Oncogene
Rhiannon K Beckers, Christina Selinger, Ricardo Vilain, Jason Madore, James S Wilmott, Kate Harvey, Anne Holliday, Caroline L Cooper, Elizabeth Robbins, David Gillet, Catherine W Kennedy, Laurence Gluch, Hugh Carmalt, Cindy Mak, Sanjay Warrier, Harriet E Gee, Charles Chan, Anna McLean, Emily Walker, Catriona M McNeil, Jane M Beith, Alexander Swarbrick, Richard A Scolyer, Sandra A O'Toole
No abstract text is available yet for this article.
February 2016: Pathology
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
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
Toshiko Kamata, Akane Suzuki, Naoko Mise, Fumie Ihara, Mariko Takami, Yuji Makita, Atsushi Horinaka, Kazuaki Harada, Naoki Kunii, Shigetoshi Yoshida, Ichiro Yoshino, Toshinori Nakayama, Shinichiro Motohashi
The role of invariant natural killer T (iNKT) cells in antitumor immunity has been studied extensively, and clinical trials in patients with advanced cancer have revealed a prolonged survival in some cases. In recent years, humanized blocking antibodies against co-stimulatory molecules such as PD-1 have been developed. The enhancement of T cell function is reported to improve antitumor immunity, leading to positive clinical effects. However, there are limited data on the role of PD-1/programmed death ligand (PDL) molecules in human iNKT cells...
September 15, 2016: Cancer Immunology, Immunotherapy: CII
Solène-Florence Kammerer-Jacquet, Laurence Crouzet, Angélique Brunot, Julien Dagher, Adélaïde Pladys, Julien Edeline, Brigitte Laguerre, Benoit Peyronnet, Romain Mathieu, Grégory Verhoest, Jean-Jacques Patard, Alexandra Lespagnol, Jean Mosser, Marc Denis, Yosra Messai, Sophie Gad-Lapiteau, Salem Chouaib, Marc-Antoine Belaud-Rotureau, Karim Bensalah, Nathalie Rioux-Leclercq
Clear cell renal cell carcinoma (ccRCC) is an aggressive tumor that is characterized in most cases by inactivation of the tumor suppressor gene VHL. The VHL/HIF/VEGF pathway thus plays a major role in angiogenesis and is currently targeted by anti-angiogenic therapy. The emergence of resistance is leading to the use of targeted immunotherapy against immune checkpoint PD1/PDL1 that restores antitumor immune response. The correlation between VHL status and PD-L1 expression has been little investigated. In this study, we retrospectively reviewed 98 consecutive cases of ccRCC and correlated PD-L1 expression by immunohistochemistry (IHC) with clinical data (up to 10-year follow-up), pathological criteria, VEGF, PAR-3, CAIX and PD-1 expressions by IHC and complete VHL status (deletion, mutation and promoter hypermethylation)...
September 13, 2016: International Journal of Cancer. Journal International du Cancer
Kaixuan Zeng, Zhe Wang, Koichi Ohshima, Yixiong Liu, Weichen Zhang, Lu Wang, Linni Fan, Mingyang Li, Xia Li, Yingmei Wang, Zhou Yu, Qingguo Yan, Shuangping Guo, Jie Wei, Ying Guo
Langerhans cell histiocytosis (LCH) is a neoplasm of myeloid origin characterized by a clonal proliferation of CD1a(+)/CD207(+) dendritic cells. Recurrent BRAF V600E mutation has been reported in LCH. In the present report, we confirm the feasibility of the high-specificity monoclonal antibody VE1 for detecting BRAF V600E mutation in 36/97 (37.1%) retrospectively enrolled patients with LCH; concordant immunohistochemistry and Sanger sequencing results were seen in 94.8% of cases. We then assessed the tumor immune microenvironment status in LCH, and found that the GATA binding protein 3 (GATA3)(+)/T-bet(+) ratio could distinguish between clinical multi-system/single-system (SS) multifocal and SS unifocal LCH...
July 2016: Oncoimmunology
Smriti Sharma, Richard E Davis, Shweta Srivastva, Susanne Nylén, Shyam Sundar, Mary E Wilson
BACKGROUND:  Visceral leishmaniasis (VL) is a potentially fatal parasitic disease associated with fever, cachexia and impaired protective T-cell responses against the parasite. METHODS:  Peripheral blood leukocytes from 105 subjects with VL and healthy control subjects from the endemic region of Muzaffarpur, Bihar, India, were compared using flow cytometry and reverse-transcriptase quantitative polymerase chain reaction. Findings were correlated with clinical data...
September 6, 2016: Journal of Infectious Diseases
Crispin T Hiley, John Le Quesne, George Santis, Rowena Sharpe, David Gonzalez de Castro, Gary Middleton, Charles Swanton
Lung cancer diagnostics have progressed greatly in the previous decade. Development of molecular testing to identify an increasing number of potentially clinically actionable genetic variants, using smaller samples obtained via minimally invasive techniques, is a huge challenge. Tumour heterogeneity and cancer evolution in response to therapy means that repeat biopsies or circulating biomarkers are likely to be increasingly useful to adapt treatment as resistance develops. We highlight some of the current challenges faced in clinical practice for molecular testing of EGFR, ALK, and new biomarkers such as PDL1...
September 3, 2016: Lancet
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
George Yaghmour, Philippe Prouet, Eric Wiedower, Omer Hassan Jamy, Rebecca Feldman, Jason C Chandler, Manjari Pandey, Mike G Martin
BACKGROUND: As we have previously reported, small cell carcinoma of the ovary (SCCO) is a rare, aggressive form of ovarian cancer associated with poor outcomes. In an effort to identify new treatment options, we utilized comprehensive genomic profiling to assess the potential for novel therapies in SCCO. METHODS: Patients with SCCO, SCCO-HT (hypercalcemic type), neuroendocrine tumors of the ovary (NET-O), and small cell carcinoma of the lung (SCLC) profiled by Caris Life Sciences between 2007-2015 were identified...
2016: Journal of Ovarian Research
H Semper, F Muehlberg, J Schulz-Menger, M Allewelt, C Grohé
Immunotherapy such as nivolumab is a new promising therapeutic option for advanced stage non small cell lung cancer (NSCLC). Due to the interference with the immune system previously unknown side effects are observed both in clinical studies and experience. Autoimmune phenomena effecting skin, gastrointestinal tract, endocrine glands, kidney and lung have been described. Up to now there is only limited information regarding potential cardiac side effects. We present a case of symptomatic drug induced myocarditis after nine cycles of nivolumab in a patient with efficient anticancer response...
September 2016: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
Zhiwei Ma, Xiao Wang, Yanling Sun, Juntao Liu, Yan Tong, Zhijing Liu
Based on the Pd(0)-catalyzed Tsuji-Trost allylic oxidative insertion reaction, we developed a fluorescent probe PdL1 for sensing Pd(0). As expected, probe PdL1 exhibited high selectivity and excellent sensitivity in both absorbance and fluorescence detection of Pd(0) in CH3CH2OH/PBS (10 mM, pH = 7.4, 6:4, v/v) solution. The detection limit was calculated to be as low as 15 nM, which can meet the selective requirements for practical application.
August 12, 2016: Journal of Fluorescence
Yanyan Bao, Xin Pan, Yahong Jin, Yingjie Gao, Xiaolan Cui
Chinese medicines (CMs) have been shown to have some advantages in preventing and controlling tumors. In this study, we investigated the antitumor effect of ZFSC by establishing a mouse model of HT-1080, A-549, and HCT-8 tumors. The result showed that tumor volumes of HT-1080 tumor-bearing nude mice in ZFSC low, medium, and high dose groups were lower significantly compared to the model group, and the high dose ZFSC showed the best antitumor effect. Tumor volumes of A-549 tumor-bearing nude mice in ZFSC low, medium, and high dose groups were lower significantly compared to the model group and showed a good dose-response relationship...
2016: Evidence-based Complementary and Alternative Medicine: ECAM
Haoting Hsu, Sarah Boudova, Godfrey Mvula, Titus H Divala, Randy G Mungwira, Christopher Harman, Miriam K Laufer, C David Pauza, Cristiana Cairo
A successful pregnancy depends on the maintenance of tolerance at the fetal-maternal interface; strong inflammation in the placental bed is generally associated with adverse fetal outcomes. Among the mechanisms that foster tolerance and limit inflammation, the fetal immune system favors Th2 or regulatory responses over Th1 responses. The unintended consequence of this functional program is high susceptibility to infections. Human Vδ2 T cells mount innate-like responses to a broad range of microorganisms and are poised for Th1 responses before birth...
September 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Ioannis Karydis, Pui Ying Chan, Matthew Wheater, Edurne Arriola, Peter W Szlosarek, Christian H Ottensmeier
BACKGROUND: Untreated metastatic uveal melanoma (UM) carries a grave prognosis. Unlike cutaneous melanoma (CM), there are no established treatments known to significantly improve outcomes for a meaningful proportion of patients. Inhibition of the PD1-PDL1 axis has shown promise in the management of CM and we here report a two center experience of UM patients receiving pembrolizumab. METHODS: To assess the efficacy and safety of pembrolizumab, we retrospectively analyzed outcome data of 25 consecutive UM patients participating in the MK3475 expanded access program (EAP) who received pembrolizumab at 2 mg/kg 3 weekly...
May 2016: Oncoimmunology
Emmanouil Papasavvas, Lea F Surrey, Deborah K Glencross, Livio Azzoni, Jocelin Joseph, Tanvier Omar, Michael D Feldman, Anna-Lise Williamson, Maureen Siminya, Avril Swarts, Xiangfan Yin, Qin Liu, Cynthia Firnhaber, Luis J Montaner
Persistence of human papillomavirus (HPV) and cervical disease in the context of HIV co-infection can be influenced by introduction of antiretroviral therapy (ART) and sustained immune activation despite ART. We conducted a cross-sectional study in order to evaluate immune activation/exhaustion in ART-suppressed HIV(+) women with or without high-risk (HR) HPV-related cervical intraepithelial neoplasia (CIN). 55 South African women were recruited in three groups: HR (-) (n = 16) and HR (+) (n = 15) HPV with negative cervical histopathology, and HR (+) HPV with CIN grade 1/2/3 (n = 24)...
May 2016: Oncoimmunology
George Yaghmour, Manjari Pandey, Catherine Ireland, Kruti Patel, Sara Nunnery, Daniel Powell, Scott Baum, Eric Wiedower, Lee S Schwartzberg, Michael G Martin
AIM: We evaluated whether tumor genome sequencing to detect the number and type of alterations could be used as a valuable biomarker for judging the potential utility of immune checkpoint inhibitors in patients with advanced cancers. MATERIALS AND METHODS: We identified patients with solid tumors who were treated with checkpoint inibitors and had received commercially available next generation sequencing (NGS). Tumors profiled by Caris Life Sciences, Foundation Medicine and Guardant360 between 2013 and 2015...
August 2016: Anticancer Research
Alessandra Bearz, Tiziana Perin, Luca Cancian, Eleonora Berto, Ivana Sartor, Umberto Tirelli
BACKGROUND: Treatment of metastatic NSCLC patients with immune-checkpoint medicine is intriguing for the potential efficacy; however it may be difficult to evaluate the clinical response due to the lack of reliable immune-monitoring markers up to now and the possibility of radiological pseudo-progression. CASE PRESENTATION: Herein we report the case of a patient ex-smoker with adenocarcinoma of the lung, stage IV for liver metastases, in progression after cisplatin-based chemotherapy and treated with antiPD-L1 (MPDL3802-Roche Genentech) e...
2016: BMC Research Notes
Jacob R Bledsoe, Robert A Redd, Robert P Hasserjian, Jacob D Soumerai, Ha T Nishino, Daniel F Boyer, Judith A Ferry, Lawrence R Zukerberg, Nancy Lee Harris, Jeremy S Abramson, Aliyah R Sohani
Primary mediastinal large B-cell lymphoma (PMBL) is a distinct subtype of diffuse large B-cell lymphoma (DLBCL) that shows overlap with classical Hodgkin lymphoma (CHL) and a favorable prognosis compared to mediastinal gray-zone lymphoma (MGZL). We performed immunohistochemistry on initial diagnostic specimens of 49 cases of uniformly treated PMBL to determine the frequency and clinical significance of expression of antigens commonly seen in CHL and MGZL, along with markers previously shown to be prognostic in DLBCL, not otherwise specified...
October 2016: American Journal of Hematology
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