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https://www.readbyqxmd.com/read/27920662/possible-noninvasive-biomarker-of-eosinophilic-esophagitis-clinical-and-experimental-evidence
#1
Sathisha Upparahalli Venkateshaiah, Murli Manohar, Alok K Verma, Uwe Blecker, Anil Mishra
Eosinophilic esophagitis (EoE) diagnosis and follow-up response to therapy is based on repeated endoscopies and histological examination for eosinophils/HPF. The procedure is invasive and risky in particular for the pediatric population. Presently, there is no highly sensitive and specific noninvasive blood test available to monitor the disease pathogenesis. Reports indicate the expression of PDL1 (CD274) on the eosinophils in allergic patients. Herein, we report that CD274-expressing and -nonexpressing eosinophils were detected in both examined pediatric and adult EoE patients...
September 2016: Case Reports in Gastroenterology
https://www.readbyqxmd.com/read/27912061/tumor-interferon-signaling-regulates-a-multigenic-resistance-program-to-immune-checkpoint-blockade
#2
Joseph L Benci, Bihui Xu, Yu Qiu, Tony J Wu, Hannah Dada, Christina Twyman-Saint Victor, Lisa Cucolo, David S M Lee, Kristen E Pauken, Alexander C Huang, Tara C Gangadhar, Ravi K Amaravadi, Lynn M Schuchter, Michael D Feldman, Hemant Ishwaran, Robert H Vonderheide, Amit Maity, E John Wherry, Andy J Minn
Therapeutic blocking of the PD1 pathway results in significant tumor responses, but resistance is common. We demonstrate that prolonged interferon signaling orchestrates PDL1-dependent and PDL1-independent resistance to immune checkpoint blockade (ICB) and to combinations such as radiation plus anti-CTLA4. Persistent type II interferon signaling allows tumors to acquire STAT1-related epigenomic changes and augments expression of interferon-stimulated genes and ligands for multiple T cell inhibitory receptors...
December 1, 2016: Cell
https://www.readbyqxmd.com/read/27900363/integration-of-genomics-and-histology-revises-diagnosis-and-enables-effective-therapy-of-refractory-cancer-of-unknown-primary-with-pdl1-amplification
#3
Stefan Gröschel, Martin Bommer, Barbara Hutter, Jan Budczies, David Bonekamp, Christoph Heining, Peter Horak, Martina Fröhlich, Sebastian Uhrig, Daniel Hübschmann, Christina Geörg, Daniela Richter, Nicole Pfarr, Katrin Pfütze, Stephan Wolf, Peter Schirmacher, Dirk Jäger, Christof von Kalle, Benedikt Brors, Hanno Glimm, Wilko Weichert, Albrecht Stenzinger, Stefan Fröhling
Identification of the tissue of origin in cancer of unknown primary (CUP) poses a diagnostic challenge and is critical for directing site-specific therapy. Currently, clinical decision-making in patients with CUP primarily relies on histopathology and clinical features. Comprehensive molecular profiling has the potential to contribute to diagnostic categorization and, most importantly, guide CUP therapy through identification of actionable lesions. We here report the case of an advanced-stage malignancy initially mimicking poorly differentiated soft-tissue sarcoma that did not respond to multiagent chemotherapy...
November 2016: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/27895920/pd1-pd-l1-inhibition-as-a-potential-radiosensitizer-in-head-and-neck-squamous-cell-carcinoma-a-case-report
#4
Misako Nagasaka, Mark Zaki, Harold Kim, S Naweed Raza, George Yoo, Ho-Sheng Lin, Ammar Sukari
BACKGROUND: Immunotherapy targeting the checkpoint PD1 (programmed cell death protein 1) or PDL1 (programmed death ligand 1) has led to advances in the treatment of melanoma and non-small cell lung cancer (NSCLC). The use of such therapies has also been introduced into the treatment of other malignancies, including head and neck cancer. The combined effects of checkpoint inhibitors and anti-PD1(L1) antibodies and radiation therapy have not yet been sufficiently investigated. CASE PRESENTATION: We report a case of locally relapsed non-resectable oral cavity squamous cell carcinoma, with excellent local control after pembrolizumab (MK3475) followed by radiotherapy...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27886124/advances-in-cancer-immunotherapy-in-solid-tumors
#5
REVIEW
Smitha Menon, Sarah Shin, Grace Dy
Immunotherapy is heralded as one of the most important advances in oncology. Until recently, only limited immunotherapeutic options were available in selected immunogenic cancers like melanoma and renal cell carcinomas. Nowadays, there is an improved understanding that anti-tumor immunity is controlled by a delicate balance in the tumor microenvironment between immune stimulatory and immune inhibitory pathways. Either by blocking the inhibitory pathways or stimulating the activating pathways that regulate cytotoxic lymphocytes, anti-tumor immunity can be enhanced leading to durable anti-tumor responses...
November 24, 2016: Cancers
https://www.readbyqxmd.com/read/27854242/the-future-prospects-of-immune-therapy-in-gastric-and-esophageal-adenocarcinoma
#6
REVIEW
Walid L Shaib, Jean Paul A Nammour, Harpaul Gill, Mayur Mody, Nabil F Saba
The prognosis of esophageal cancers is poor and novel approaches are urgently needed. Despite improvements in outcomes with transtuzumab and ramucirumab, these improvements added an average of only 2 to 3 months with a median overall survival reported to be around 1 year. Comprehensive genomic sequencing has defined some molecular alterations with potential targets, but the majority of patients still do not benefit from druggable targets. Breakthroughs in immune checkpoint blockade have provided new therapeutic options in many cancers...
November 14, 2016: Journal of Clinical Medicine
https://www.readbyqxmd.com/read/27827885/is-there-still-room-for-cancer-vaccines-at-the-era-of-checkpoint-inhibitors
#7
REVIEW
Soumaya Karaki, Marie Anson, Thi Tran, Delphine Giusti, Charlotte Blanc, Stephane Oudard, Eric Tartour
Checkpoint inhibitor (CPI) blockade is considered to be a revolution in cancer therapy, although most patients (70%-80%) remain resistant to this therapy. It has been hypothesized that only tumors with high mutation rates generate a natural antitumor T cell response, which could be revigorated by this therapy. In patients with no pre-existing antitumor T cells, a vaccine-induced T cell response is a rational option to counteract clinical resistance. This hypothesis has been validated in preclinical models using various cancer vaccines combined with inhibitory pathway blockade (PD-1-PDL1-2, CTLA-4-CD80-CD86)...
November 3, 2016: Vaccines
https://www.readbyqxmd.com/read/27821490/suppression-of-type-i-ifn-signaling-in-tumors-mediates-resistance-to-anti-pd-1-treatment-that-can-be-overcome-by-radiotherapy
#8
Xiaohong Wang, Jonathan E Schoenhals, Ailin Li, David R Valdecanas, Huiping Ye, Fenglin Zhang, Chad Tang, Ming Tang, Chang-Gong Liu, Xiuping Liu, Sunil Krishnan, James P Allison, Padmanee Sharma, Patrick Hwu, Ritsuko Komaki, Willem W Overwijk, Daniel R Gomez, Joe Y Chang, Stephen M Hahn, Maria Angelica Cortez, James W Welsh
Immune checkpoint therapies exhibit impressive efficacy in some patients with melanoma or lung cancer, but the lack of response in most cases presses the question of how general efficacy can be improved. In addressing this question, we generated a preclinical tumor model to study anti-PD-1 resistance by in vivo passaging of Kras-mutated, p53-deficient murine lung cancer cells (p53R172HΔg/+K-rasLA1/+) in a syngeneic host exposed to repetitive dosing with anti-mouse PD-1 antibodies. PDL1 (CD274) expression did not differ between the resistant and parental tumor cells...
November 7, 2016: Cancer Research
https://www.readbyqxmd.com/read/27819282/characterization-of-t-follicular-helper-cells-in-allogeneic-normal-pregnancy-and-pdl1-blockage-induced-abortion
#9
Weihong Zeng, Zhicui Liu, Siming Zhang, Jiabin Ren, Xiaoling Ma, Chuanmei Qin, Fuju Tian, Yan Zhang, Yi Lin
A deeper understanding of the immunological events during pregnancy will provide novel insights into the pathogenesis of pregnancy complications. The fundamental function of T follicular helper (Tfh) cells is to provide cognate help to B cells. Dysregulations of Tfh-cell function and/or development can result in various immunological diseases. However, the role and characteristics of Tfh cells during pregnancy remain unknown. Herein, an allogeneic-normal-pregnant mouse model was used, and we found that the CD4(+) T cells residing at the uterus and placenta (UP) displayed a Tfh-like phenotype; and the UP-derived CD4(+)CXCR5(hi)PD-1(hi) and CD4(+)CXCR5(hi)ICOS(hi) Tfh cells, which showed a memory/activation phenotype, reached their peak at mid-pregnancy...
November 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27808592/pd1-and-pdl1-upregulation-and-survival-after-decitabine-treatment-in-lower-risk-mds
#10
Sameem Abedin, Leonidas C Platanias
No abstract text is available yet for this article.
November 3, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27802341/acute-malaria-induces-pd1-ctla4-effector-t-cells-with-cell-extrinsic-suppressor-function
#11
Maria Sophia Mackroth, Annemieke Abel, Christiane Steeg, Julian Schulze Zur Wiesch, Thomas Jacobs
In acute Plasmodium falciparum (P. falciparum) malaria, the pro- and anti-inflammatory immune pathways must be delicately balanced so that the parasitemia is controlled without inducing immunopathology. An important mechanism to fine-tune T cell responses in the periphery is the induction of coinhibitory receptors such as CTLA4 and PD1. However, their role in acute infections such as P. falciparum malaria remains poorly understood. To test whether coinhibitory receptors modulate CD4+ T cell functions in malaria, blood samples were obtained from patients with acute P...
November 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27775076/multiplatform-based-molecular-subtypes-of-non-small-cell-lung-cancer
#12
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
https://www.readbyqxmd.com/read/27772919/pdl1-expression-in-triple-negative-breast-cancer-is-associated-with-tumour-infiltrating-lymphocytes-and-improved-outcome
#13
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
https://www.readbyqxmd.com/read/27769776/immunotherapy-of-lung-malignancies-from-gene-sequencing-to-novel-therapies
#14
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
https://www.readbyqxmd.com/read/27754760/combining-mpdl3280a-with-adoptive-cell-immunotherapy-exerts-better-antitumor-effects-against-cervical-cancer
#15
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
https://www.readbyqxmd.com/read/27631416/blockade-of-programmed-death-1-programmed-death-ligand-pathway-enhances-the-antitumor-immunity-of-human-invariant-natural-killer-t-cells
#16
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...
December 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27623354/independent-association-of-pd-l1-expression-with-noninactivated-vhl-clear-cell-renal-cell-carcinoma-a-finding-with-therapeutic-potential
#17
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)...
January 1, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27622040/braf-v600e-mutation-correlates-with-suppressive-tumor-immune-microenvironment-and-reduced-disease-free-survival-in-langerhans-cell-histiocytosis
#18
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
https://www.readbyqxmd.com/read/27601622/a-subset-of-neutrophils-expressing-markers-of-antigen-presenting-cells-in-human-visceral-leishmaniasis
#19
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...
November 15, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27598680/challenges-in-molecular-testing-in-non-small-cell-lung-cancer-patients-with-advanced-disease
#20
REVIEW
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
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