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https://www.readbyqxmd.com/read/30321406/the-immune-landscape-of-prostate-cancer-and-nomination-of-pd-l2-as-a-potential-therapeutic-target
#1
Shuang G Zhao, Jonathan Lehrer, S Laura Chang, Rajdeep Das, Nicholas Erho, Yang Liu, Martin Sjöström, Robert B Den, Stephen J Freedland, Eric A Klein, R Jeffrey Karnes, Edward M Schaeffer, Melody Xu, Corey Speers, Paul L Nguyen, Ashley E Ross, June M Chan, Matthew R Cooperberg, Peter R Carroll, Elai Davicioni, Lawrence Fong, Daniel E Spratt, Felix Y Feng
Background: Immunotherapy has been less successful in treating prostate cancer than other solid tumors. We sought to better understand the immune landscape in prostate cancer and identify immune-related biomarkers and potential therapeutic targets. Methods: We analyzed gene expression data from 7826 prospectively collected prostatectomy samples (2013-2016), and 1567 retrospective samples with long-term clinical outcomes, for a total of 9393 samples, all profiled on the same commercial clinical platform in a CLIA-certified lab...
October 13, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/30319128/-immunotherapy-in-castration-resistant-prostate-cancer
#2
Bernardino Miñana López, Felipe Villacampa Aubá, Fernando Ramón de Fata Chillón, Francisco Javier Ancizu Markert, Angel García Cortés, Pablo Doménech López, Santiago Chiva San Román, José María Velis Campillo, Fernando Díez-Caballero Alonso, José Enrique Robles García, David Rosell Costa, Juan Ignacio Pascual Piédrola
We review the role of immunotherapy in castration resistant prostate cancer. Two immunotherapeutic strategies have been applied, isolated or in combination, either with each other or with other agents with demonstrated efficacy in this scenario that would play a role as immunomodulators: vaccines or monoclonal antibodies aimed to block immune response checkpoint inhibitors. Although CRPC presents, a priori, characteristics suggesting that immunotherapy may play a relevant role as a therapeutic strategy, its clinical application has demonstrated a limited and heterogeneous activity, in terms of proportion of responders and response intensity...
September 2018: Archivos Españoles de Urología
https://www.readbyqxmd.com/read/30318169/serum-concentrations-of-hgf-are-correlated-with-response-to-anti-pd-1-antibody-therapy-in-patients-with-metastatic-melanoma
#3
Yosuke Kubo, Satoshi Fukushima, Yukiko Inamori, Mina Tsuruta, Sho Egashira, Saori Yamada-Kanazawa, Satoshi Nakahara, Aki Tokuzumi, Azusa Miyashita, Jun Aoi, Ikko Kajihara, Yusuke Tomita, Kazumasa Wakamatsu, Masatoshi Jinnin, Hironobu Ihn
BACKGROUND: Anti-programmed cell death protein (PD)-1 antibody treatment is associated with a notable improvement in only 30%-40% of patients. Thus, a predictive and easily measured marker of the clinical benefit of anti-PD-1 antibody treatment is necessary; therefore, in this study, we focused on the serum concentration of hepatocyte growth factor (HGF). OBJECTIVES: To evaluate whether the serum concentration of HGF can be used as a biomarker for the clinical response to anti-PD-1 antibody therapy...
October 6, 2018: Journal of Dermatological Science
https://www.readbyqxmd.com/read/30318080/nimotuzumab-beyond-the-egfr-signaling-cascade-inhibition
#4
REVIEW
Zaima Mazorra, Lisset Chao, Anabel Lavastida, Belinda Sanchez, Mayra Ramos, Normando Iznaga, Tania Crombet
One of the most known oncogenes is the epidermal growth factor receptor (EGFR) family. It activates multiple signaling cascades that promote carcinogenesis and immune evasion. Therefore, these molecules have been extensively targeted in cancer immunotherapy. Beyond EGFR signaling cascade inhibition, some of these agents are able to induce T-cell activation, transforming a passive therapy into a vaccine-like effect. Nimotuzumab is an IgG1 humanized monoclonal antibody directed against the extracellular domain of the EGFR blocking the binding to its ligands...
January 2018: Seminars in Oncology
https://www.readbyqxmd.com/read/30317583/predictive-and-therapeutic-biomarkers-in-chimeric-antigen-receptor-t-cell-therapy-a-clinical-perspective
#5
REVIEW
Hamid Reza Mirzaei, Hamed Mirzaei, Afshin Namdar, Majid Rahmati, Brian G Till, Jamshid Hadjati
The adoptive transfer of genetically engineered T cells modified to express a chimeric antigen receptor (CAR) has shown remarkable activity and induces long-term remissions in patients with advanced hematologic malignancies. To date, little is known about predictive indicators of therapeutic efficacy or serious toxicity after CAR T-cell therapy in clinical practice. Biomarkers are not only potentially able to inform physicians and researchers of immunotherapy targets in particular but could also be used to monitor the effectiveness of treatments and to predict incidence of side effects in some circumstances...
October 14, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/30317464/gene-expression-profile-of-peripheral-blood-mononuclear-cells-may-contribute-to-the-identification-and-immunological-classification-of-breast-cancer-patients
#6
Eiji Suzuki, Masahiro Sugimoto, Kosuke Kawaguchi, Fengling Pu, Ryuji Uozumi, Ayane Yamaguchi, Mariko Nishie, Moe Tsuda, Takeshi Kotake, Satoshi Morita, Masakazu Toi
BACKGROUND: It has been reported that the gene expression profile of peripheral blood mononuclear cells (PBMCs) exhibits a unique gene expression signature in several types of cancer. In this study, we aimed to explore the breast cancer patient-specific gene expression profile of PBMCs and discuss immunological insight on host antitumor immune responses. METHODS: We comprehensively analyzed the gene expression of PBMCs by RNA sequencing in the breast cancer patients as compared to that of healthy volunteers (HVs)...
October 13, 2018: Breast Cancer: the Journal of the Japanese Breast Cancer Society
https://www.readbyqxmd.com/read/30317163/potential-regulatory-roles-of-micrornas-and-long-noncoding-rnas-in-anticancer-therapies
#7
REVIEW
Mengyan Xie, Ling Ma, Tongpeng Xu, Yutian Pan, Qiang Wang, Yutian Wei, Yongqian Shu
MicroRNAs and long noncoding RNAs have long been investigated due to their roles as diagnostic and prognostic biomarkers of cancers and regulators of tumorigenesis, and the potential regulatory roles of these molecules in anticancer therapies are attracting increasing interest as more in-depth studies are performed. The major clinical therapies for cancer include chemotherapy, immunotherapy, and targeted molecular therapy. MicroRNAs and long noncoding RNAs function through various mechanisms in these approaches, and the mechanisms involve direct targeting of immune checkpoints, cooperation with exosomes in the tumor microenvironment, and alteration of drug resistance through regulation of different signaling pathways...
September 1, 2018: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/30315134/evaluation-of-a-novel-liquid-biopsy-based-coloscape-assay-for-mutational-analysis-of-colorectal-neoplasia-and-triage-of-fit-patients-a-pilot-study
#8
Mauro Scimia, Jinwei Du, Francesco Pepe, Maria Antonia Bianco, Silvana Russo Spena, Farah Patell-Socha, Qing Sun, Michael J Powell, Umberto Malapelle, Giancarlo Troncone
Circulating cell free tumour derived nucleic acids are becoming recognised as clinically significant and extremely useful biomarkers for detection of cancer and for monitoring the progression of targeted drug therapy and immunotherapy. Screening programmes for colorectal cancer in Europe use the Fetal Immunochemical Test (FIT) test as a primary screener. FIT+ patients are referred to immediate colonoscopy and the positive predictive value (PPV) is usually 25%. In this article, we report a study employing the ColoScape assay panel to detect mutations in the APC, KRAS, BRAF and CTNNB1 genes, in order to collect preliminary performance indicators and plan a future, larger population study...
October 12, 2018: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/30309915/pan-tumor-genomic-biomarkers-for-pd-1-checkpoint-blockade-based-immunotherapy
#9
Razvan Cristescu, Robin Mogg, Mark Ayers, Andrew Albright, Erin Murphy, Jennifer Yearley, Xinwei Sher, Xiao Qiao Liu, Hongchao Lu, Michael Nebozhyn, Chunsheng Zhang, Jared K Lunceford, Andrew Joe, Jonathan Cheng, Andrea L Webber, Nageatte Ibrahim, Elizabeth R Plimack, Patrick A Ott, Tanguy Y Seiwert, Antoni Ribas, Terrill K McClanahan, Joanne E Tomassini, Andrey Loboda, David Kaufman
Programmed cell death protein-1 (PD-1) and programmed cell death ligand-1 (PD-L1) checkpoint blockade immunotherapy elicits durable antitumor effects in multiple cancers, yet not all patients respond. We report the evaluation of >300 patient samples across 22 tumor types from four KEYNOTE clinical trials. Tumor mutational burden (TMB) and a T cell-inflamed gene expression profile (GEP) exhibited joint predictive utility in identifying responders and nonresponders to the PD-1 antibody pembrolizumab. TMB and GEP were independently predictive of response and demonstrated low correlation, suggesting that they capture distinct features of neoantigenicity and T cell activation...
October 12, 2018: Science
https://www.readbyqxmd.com/read/30308466/molecular-imaging-to-enlighten-cancer-immunotherapies-and-underlying-involved-processes
#10
REVIEW
Elly L van der Veen, Frederike Bensch, Andor W J M Glaudemans, Marjolijn N Lub-de Hooge, Elisabeth G E de Vries
Cancer immunotherapy has led to impressive antitumor effects. However, not all patients respond to immunotherapy, serious toxicity can occur and combination therapy may be warranted. Strategies for rational early treatment choices are urgently required. In the absence of ideal accompanying biomarkers it remains challenging to capture the dynamic, heterogeneous and complex tumor behavior. Tumor immune response involves next to tumor cells, numerous other cells and molecules in the tumor microenvironment. We review research to identify potential novel imaging biomarkers by non-invasive whole body molecular imaging with positron emission tomography and single-photon emission computed tomography for cancer immunotherapy...
September 25, 2018: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/30307465/-personalized-biomarker-based-treatment-strategy-for-patients-with-squamous-cell-carcinoma-of-the-head-and-neck-eortc-position-and-approach
#11
R Galot, C Le Tourneau, J Guigay, L Licitra, I Tinhofer, A Kong, C Caballero, C Fortpied, J Bogaerts, A-S Govaerts, D Staelens, T Raveloarivahy, L Rodegher, J-F Laes, E Saada-Bouzid, J-P Machiels
The molecular landscape of squamous cell carcinoma of the head and the neck (SCCHN) has been characterized and actionable or targetable genomic alterations have been identified. However, targeted therapies have very limited activity in unselected SCCHN and the current treatment strategy is still based on tumor location and disease stage and not on tumor biology.Trying to select upfront the patients who will benefit from a specific treatment might be a way to improve patients' outcome. With the objective of optimizing the activity of targeted therapies and immunotherapy, we have designed an umbrella biomarker-driven study dedicated to recurrent and/or metastatic SCCHN patients (EORTC-1559-HNCG, NCT03088059)...
October 11, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/30307119/clinical-proteomics-for-post-hematopoeitic-stem-cell-transplantation-outcomes
#12
REVIEW
Sophie Paczesny, Jochen Metzger
Allogeneic hematopoietic stem cell transplantation (HSCT) is the most effective form of tumor immunotherapy available to date. However, while HSCT can induce beneficial graft-versus-leukemia (GVL) effect, the adverse effect of graft-versus-host disease (GVHD), which is closely linked to GVL, is the major source of morbidity and mortality following HSCT. Until recently, available diagnostic and staging tools frequently fail to identify those at higher risk of disease progression or death. Furthermore, there are shortcomings in the prediction of the need for therapeutic interventions or the response rates to different forms of therapy...
October 11, 2018: Proteomics. Clinical Applications
https://www.readbyqxmd.com/read/30306576/targeted-therapy-for-gynecologic-cancers-toward-the-era-of-precision-medicine
#13
Partha Basu, Asima Mukhopadhyay, Ikuo Konishi
Recent advances in molecular biology of cancer have led to the development of targeted agents, mainly of monoclonal antibodies and small-molecule compounds. Unlike traditional drugs that inhibit DNA synthesis and mitosis, these agents target the signaling pathways of cancer cells, stroma, and vasculature in tumor tissues. For gynecologic cancers, drugs targeting angiogenesis such as anti-VEGF antibody have been used in the treatment of advanced or recurrent ovarian and cervical cancers, and the drugs targeting homologous recombination deficiency such as PARP inhibitors have been approved for maintenance after chemotherapy in platinum-sensitive ovarian cancer...
October 2018: International Journal of Gynaecology and Obstetrics
https://www.readbyqxmd.com/read/30302387/eus-fine-needle-pancreatic-core-biopsy-can-determine-eligibility-for-tumor-agnostic-immunotherapy
#14
Ferga C Gleeson, Michael J Levy, Anja C Roden, Lisa A Boardman, Frank A Sinicrope, Robert R McWilliams, Lizhi Zhang
Background and study aims  The US FDA recently approved a cancer treatment with pembrolizumab based upon the tumor biomarker status of deficient mismatch repair (dMMR) rather than a specific disease-based approach. We sought to determine if endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) could determine dMMR and quantification of PD-L1 expression to potentially guide the delivery of tumor agnostic immunotherapy. Patients and methods  Immunohistochemistry was performed on archived pancreas core biopsy specimens...
October 2018: Endoscopy International Open
https://www.readbyqxmd.com/read/30299387/innate-immune-cell-infiltration-in-melanoma-metastases-affects-survival-and-is-associated-with-brafv600e-mutation-status
#15
Nina Dabrosin, Karen Sloth Juul, Jeanette Bæhr Georgsen, Simon Andrup, Henrik Schmidt, Torben Steiniche, Trine Heide Øllegaard, Louise Bønnelykke Behrndtz
Little is known about the infiltrative pattern of innate immune cells in primary melanoma compared with their paired metastases and in BRAF-mutated tumors. Therefore, our aim was to characterize the inflammatory microenvironment in primary ulcerated and nonulcerated melanomas and paired metastases, to investigate the relation between inflammation and BRAF mutation in primary melanoma and paired metastases, and to evaluate the effect of the analyzed biomarkers on melanoma-specific survival. A total of 385 primary tumors and 96 paired metastases were stained with immunohistochemistry for BRAF, CD163+ macrophages, CD123+ plasmacytoid dendritic cells, CD66b+ neutrophils, and E-cadherin and estimated using objective computer-assisted image analysis...
October 5, 2018: Melanoma Research
https://www.readbyqxmd.com/read/30299021/clinical-use-of-basophil-activation-test-bat-in-drug-food-and-hymenoptera-venom-allergies
#16
Mara De Amici, Fiorella Barocci, Silvia Caimmi, Luigi Nespoli, Amelia Licari, Giuseppe Giuliani, Gianluigi Marseglia
The basophil activation is emerging as a reliable and robust in vitro biomarker of in vivo allergy reactions. Basophil Activation Test (BAT), intended as in vitro stimulation of patient blood basophil with allergens, followed by flow cytometric detection and quantification of such activation, is nowadays a well-established assay in a growing number of routine diagnostic labs. The advancements in the standardization of BAT testing and first convincing clinical evidence are behind this spreading of the assay in clinical lab...
October 4, 2018: Minerva Pediatrica
https://www.readbyqxmd.com/read/30294272/prognostic-factors-for-checkpoint-inhibitor-based-immunotherapy-an-update-with-new-evidences
#17
REVIEW
Xinyu Yan, Shouyue Zhang, Yun Deng, Peiqi Wang, Qianqian Hou, Heng Xu
Checkpoint inhibitor (CPI) based immunotherapy (i.e., anit-CTLA-4/PD-1/PD-L1 antibodies) can effectively prolong overall survival of patients across several cancer types at the advanced stage. However, only part of patients experience objective responses from such treatments, illustrating large individual differences in terms of both efficacy and adverse drug reactions. Through the observation on a series of CPI based clinical trials in independent patient cohorts, associations of multiple clinical and molecular characteristics with CPI response rate have been determined, including microenvironment, genomic alterations of the cancer cells, and even gut microbiota...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/30292142/the-fast-real-time-assessment-of-combination-therapies-in-immuno-oncology-fraction-program-innovative-high-throughput-clinical-screening-of-immunotherapies
#18
Katy L Simonsen, Paula M Fracasso, Steven H Bernstein, Megan Wind-Rotolo, Manish Gupta, Adriana Comprelli, Timothy P Reilly, Jim Cassidy
BACKGROUND: The unprecedented success of immuno-oncology (I-O) agents targeting the cytotoxic T lymphocyte-associated antigen 4 and programmed death-1/programmed death-ligand 1 pathways has stimulated the rapid development of other I-O agents against novel immune targets. Bristol-Myers Squibb has designed a novel phase II platform trial, the Fast Real-time Assessment of Combination Therapies in Immuno-ONcology (FRACTION) Program, to efficiently identify promising combinations for patients with specific malignancies...
October 3, 2018: European Journal of Cancer
https://www.readbyqxmd.com/read/30291127/better-standards-sought-for-predictive-immunotherapy-biomarkers
#19
(no author information available yet)
Predictive biomarkers of immunotherapy are growing increasingly complex-incorporating aspects of tumor-intrinsic, immune microenvironmental, and host-related biology-and several new initiatives aim to establish standards for the field to ensure consistency of commercial assays going forward.
October 5, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/30288393/intensive-combination-immunotherapy-and-neuroinflammation-resolution-in-a-child-with-anti-pca-1-yo-paraneoplastic-syndrome-and-2-malignancies
#20
Guillermo Philipps, Elizabeth D Tate, Michael R Pranzatelli
Paraneoplastic cerebellar degeneration is rare and noteworthy in children. In this 7-year-old, it was documented to have occurred within a year of ataxia presentation. The instigating cancer was stage III adrenal adenocarcinoma, remitted after surgical resection at age 2. When her severe ataxia progressed, neuroinflammation was characterized by high cerebrospinal fluid Purkinje cell cytoplasmic antibody type 1 titers, oligoclonal bands, and neurofilament light chain. The immunotherapy strategy was to replace IV methylprednisolone, which lowered Purkinje cell cytoplasmic antibody type 1 titers without clinical improvement, with induction of adrenocorticotropic hormone/intravenous immunoglobulin/rituximab (ACTH/IVIG/rituximab) combination immunotherapy, ACTH/dexamethasone transition, and intravenous immunoglobulin maintenance...
2018: Child Neurology Open
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