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https://www.readbyqxmd.com/read/28344865/identification-of-genetic-determinants-of-breast-cancer-immune-phenotypes-by-integrative-genome-scale-analysis
#1
Wouter Hendrickx, Ines Simeone, Samreen Anjum, Younes Mokrab, François Bertucci, Pascal Finetti, Giuseppe Curigliano, Barbara Seliger, Luigi Cerulo, Sara Tomei, Lucia Gemma Delogu, Cristina Maccalli, Ena Wang, Lance D Miller, Francesco M Marincola, Michele Ceccarelli, Davide Bedognetti
Cancer immunotherapy is revolutionizing the clinical management of several tumors, but has demonstrated limited activity in breast cancer. The development of more effective treatments is hindered by incomplete knowledge of the genetic determinant of immune responsiveness. To fill this gap, we mined copy number alteration, somatic mutation, and expression data from The Cancer Genome Atlas (TCGA). By using RNA-sequencing data from 1,004 breast cancers, we defined distinct immune phenotypes characterized by progressive expression of transcripts previously associated with immune-mediated rejection...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28331342/spotlight-on-atezolizumab-and-its-potential-in-the-treatment-of-advanced-urothelial-bladder-cancer
#2
REVIEW
Ahmet Murat Aydin, Solomon L Woldu, Ryan C Hutchinson, Martin Boegemann, Aditya Bagrodia, Yair Lotan, Vitaly Margulis, Laura-Maria Krabbe
Metastatic urothelial carcinoma of the bladder is an aggressive malignancy with poor prognosis, reflecting a lack of effective systemic therapies. The current standard of care includes multiagent platinum-based chemotherapy; however a majority of patients do not respond to treatment and most eventually succumb to disease. Recently, renewed interest in immunotherapy in the form of immune-checkpoint inhibition has gained widespread attention for a number of malignancies. Atezolizumab, an anti-PDL1 antibody, has been shown to be effective in a subset of patients previously treated with or unfit for platinum-based chemotherapy, and has shown durable responses with a good tolerability profile...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28325631/new-concepts-of-personalized-therapy-in-salivary-gland-carcinomas
#3
REVIEW
Gunter Keller, Diana Steinmann, Alexander Quaas, Viktor Grünwald, Stefan Janssen, Kais Hussein
Salivary gland carcinomas are rare tumours and therapy strategies are less standardized than in lung, gastric or breast cancer. Therapy is based on surgery, but not all carcinomas are completely resectable, e.g. because carcinomas often show infiltration of nerves. For further therapy decision pathology is recommended, but evaluation of potential targets for personalized therapy is not part of the routine panel. Many salivary gland carcinomas can be resistant to radio- and/or chemotherapy, which limits therapeutic options...
March 18, 2017: Oral Oncology
https://www.readbyqxmd.com/read/28325288/retroviral-replicating-vector-delivery-of-mir-pdl1-inhibits-immune-checkpoint-pdl1-and-enhances-immune-responses-in%C3%A2-vitro
#4
Amy H Lin, Christopher G Twitty, Ryan Burnett, Andrew Hofacre, Leah A Mitchell, Fernando Lopez Espinoza, Harry E Gruber, Douglas J Jolly
Tumor cells express a number of immunosuppressive molecules that can suppress anti-tumor immune responses. Efficient delivery of small interfering RNAs to treat a wide range of diseases including cancers remains a challenge. Retroviral replicating vectors (RRV) can be used to stably and selectively introduce genetic material into cancer cells. Here, we designed RRV to express shRNA (RRV-shPDL1) or microRNA30-derived shRNA (RRV-miRPDL1) using Pol II or Pol III promoters to downregulate PDL1 in human cancer cells...
March 17, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28321813/harnessing-the-immune-system-against-leukemia-monoclonal-antibodies-and-checkpoint-strategies-for-aml
#5
Lucia Masarova, Hagop Kantarjian, Guillermo Garcia-Mannero, Farhad Ravandi, Padmanee Sharma, Naval Daver
Acute myeloid leukemia (AML) is the most common leukemia among adults and is associated with a poor prognosis, especially in patients with adverse prognostic factors, older age, or relapsed disease. The last decade has seen a surge in successful immune-based therapies in various solid tumors; however, the role of immune therapies in AML remains poorly defined. This chapter describes the rationale, clinical data, and toxicity profiles of immune-based therapeutic modalities in AML including naked and conjugated monoclonal antibodies, bispecific T-cell engager antibodies, chimeric antigen receptor (CAR)-T cells, and checkpoint blockade via blockade of PD1/PDL1 or CTLA4...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28314785/tumor-localized-secretion-of-soluble-pd1-enhances-oncolytic-virotherapy
#6
Mee Y Bartee, Katherine M Dunlap, Eric Bartee
Oncolytic virotherapy represents an attractive option for the treatment of a variety of aggressive or refractory tumors. While this therapy is effective at rapidly debulking directly injected tumor masses, achieving complete eradication of established disease has proven difficult. One method to overcome this challenge is to use oncolytic viruses to induce secondary anti-tumor immune responses. Unfortunately, while the initial induction of these immune responses is typically robust, their subsequent efficacy is often inhibited through a variety of immunoregulatory mechanisms, including the PD1/PDL1 T-cell checkpoint pathway...
March 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28277834/predictive-biomarkers-along-gastric-cancer-pathogenetic-pathways
#7
Iacopo Panarese, Fernando De Vita, Andrea Ronchi, Marco Romano, Roberto Alfano, Natale Di Martino, Federica Zito Marino, Francesca Ferraraccio, Renato Franco
Gastric cancer is the second leading cause of cancer all over the world. Unfortunately, several gastric cancers are diagnosed in an advanced stage and chemotherapy and/or target therapies medical treatment remain the only options to treat patients. Areas Covered: Herein we evaluate the new molecular proposal of gastric cancer classification, offering the possibility to recognize different pathogenetic mechanisms and molecular biomarkers potentially useful for target therapies. Expert commentary: The possibility of introducing new specific tests for identification of molecular biomarkers critical for targeted therapies response represents the new frontier in the selection of gastric cancer patients to improve their survival...
March 1, 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28258692/lag3-cd223-as-a-cancer-immunotherapy-target
#8
REVIEW
Lawrence P Andrews, Ariel E Marciscano, Charles G Drake, Dario A A Vignali
Despite the impressive impact of CTLA4 and PD1-PDL1-targeted cancer immunotherapy, a large proportion of patients with many tumor types fail to respond. Consequently, the focus has shifted to targeting alternative inhibitory receptors (IRs) and suppressive mechanisms within the tumor microenvironment. Lymphocyte activation gene-3 (LAG3) (CD223) is the third IR to be targeted in the clinic, consequently garnering considerable interest and scrutiny. LAG3 upregulation is required to control overt activation and prevent the onset of autoimmunity...
March 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28258060/can-an-immune-checkpoint-inhibitor-sometimes-make-things-worse
#9
Elad Sharon
Champiat and colleagues have identified in their trial participants a group of patients that appear to have accelerated tumor progression when treated with PD1/PDL1 inhibitors. While their work is provocative, there are several limitations present in their analysis. Investigators should work quickly to verify and better characterize these results.
March 3, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28251900/immunotherapy-related-skin-toxicity-bullous-pemphigoid-in-a-lung-adenocarcinoma-patient-treated-with-the-anti-pdl1-antibody-atezolizumab
#10
Irene Russo, Giorgia Sacco, Stefano Frega, Valentina Polo, Giulia Pasello, Mauro Alaibac
No abstract text is available yet for this article.
March 1, 2017: European Journal of Dermatology: EJD
https://www.readbyqxmd.com/read/28217128/tumor-associated-lymphatic-vessels-upregulate-pdl1-to-inhibit-t-cell-activation
#11
Lothar C Dieterich, Kristian Ikenberg, Timur Cetintas, Kübra Kapaklikaya, Cornelia Hutmacher, Michael Detmar
Tumor-associated lymphatic vessels (LVs) play multiple roles during tumor progression, including promotion of metastasis and regulation of antitumor immune responses by delivering antigen from the tumor bed to draining lymph nodes (LNs). Under steady-state conditions, LN resident lymphatic endothelial cells (LECs) have been found to maintain peripheral tolerance by directly inhibiting autoreactive T-cells. Similarly, tumor-associated lymphatic endothelium has been suggested to reduce antitumor T-cell responses, but the mechanisms that mediate this effect have not been clarified...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28186088/current-status-of-immunotherapy-for-gastrointestinal-stromal-tumor
#12
REVIEW
Y Tan, J C Trent, B A Wilky, D A Kerr, A E Rosenberg
Gastrointestinal stromal tumors (GIST) contain tumor-infiltrating immune cells and their presence provides an opportunity and rationale for developing effective forms of immunotherapy. The types of tumor-infiltrating inflammatory cells and relevant immune checkpoint inhibitors are the focus of active investigation. The most numerous tumor-infiltrating inflammatory cells are tumor-associated macrophages (TAMs) and CD3+ T cells. Studies have shown that patients with GISTs that harbor increased numbers of CD3+ T cells have better outcomes...
February 10, 2017: Cancer Gene Therapy
https://www.readbyqxmd.com/read/28159915/strategies-to-overcome-bypass-mechanisms-mediating-clinical-resistance-to-egfr-tyrosine-kinase-inhibition-in-lung-cancer
#13
REVIEW
Hatim Husain, Michael Scur, Ayesha Murtuza, Nam Bui, Brian Woodward, Razelle Kurzrock
The vast majority of patients with metastatic lung cancers who initially benefit from EGFR-targeted therapies eventually develop resistance. An increasing understanding of the number and complexity of resistance mechanisms highlights the challenge of treating tumors resistant to EGFR inhibitors. Resistance mechanisms include new, second-site mutations within EGFR (e.g., T790M and C797S), upregulation of MET kinase, upregulation of insulin growth factor receptor (IGFR), HER2 amplification, increased expression of AXL, BIM modulation, NF-κB activation, histologic switch to small-cell cancer, epithelial-to-mesenchymal transition, PDL1 expression with subsequent immune tolerance, and release of cytokines such as TGFβ and IL6...
February 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28154845/deactivation-of-the-coordinating-ability-of-the-iminophosphorane-group-by-the-effect-of-ortho-carborane
#14
Pablo Crujeiras, José Luis Rodríguez-Rey, Antonio Sousa-Pedrares
The C-carboranyl iminophosphorane compounds derived from triphenylphosphine (I1) and o-(methylthiophenyl)-diphenylphosphine (I2) were obtained and structurally characterized. Functionalization with sulfur on the other cage carbon atom gave the corresponding disulfides (L1L1 and L2L2). In the case of I1 it was also possible to isolate the trisulfide (L1SL1) and the thiol (L1H), which is not in the expected zwitterionic form, showing that the carborane group reduces the basicity of the nitrogen atom. The disulfides were made to react with the zero-valent metal precursors [M(PPh3)4], where M = Pd, Pt...
February 3, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/28151378/checkpoint-inhibition-new-treatment-options-in-urologic-cancer
#15
Daan Joost De Maeseneer, Brant Delafontaine, Sylvie Rottey
Both urothelial (UC) and renal cell cancer (RCC) are highly immunogenic tumours. Recent advances in cellular immunity understanding have resulted in a successful new class of therapeutic agents. Interaction between the programmed cell death 1 (PD1) on regulatory T-cells (Treg) and programmed cell death 1 ligand (PDL1) on cancer cells inhibits an effective immune response and is an important mechanism for cancer cells to evade the immune system. Monoclonal anti-PD1 and anti-PDL1 antibodies inhibit this interaction and are called checkpoint inhibitors...
February 2017: Acta Clinica Belgica
https://www.readbyqxmd.com/read/28129117/immunosuppressive-myeloid-cells-blockade-in-the-glioma-microenvironment-enhances-the-efficacy-of-immune-stimulatory-gene-therapy
#16
Neha Kamran, Padma Kadiyala, Meghna Saxena, Marianela Candolfi, Youping Li, Mariela A Moreno-Ayala, Nicholas Raja, Diana Shah, Pedro R Lowenstein, Maria G Castro
Survival of glioma (GBM) patients treated with the current standard of care remains dismal. Immunotherapeutic approaches that harness the cytotoxic and memory potential of the host immune system have shown great benefit in other cancers. GBMs have developed multiple strategies, including the accumulation of myeloid-derived suppressor cells (MDSCs) to induce immunosuppression. It is therefore imperative to develop multipronged approaches when aiming to generate a robust anti-tumor immune response. Herein, we tested whether combining MDSC depletion or checkpoint blockade would augment the efficacy of immune-stimulatory herpes simplex type-I thymidine kinase (TK) plus Fms-like tyrosine kinase ligand (Flt3L)-mediated immune stimulatory gene therapy...
January 4, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28054442/markers-and-function-of-human-nk-cells-in-normal-and-pathological-conditions
#17
REVIEW
Genny Del Zotto, Emanuela Marcenaro, Paola Vacca, Simona Sivori, Daniela Pende, Mariella Della Chiesa, Francesca Moretta, Tiziano Ingegnere, Maria Cristina Mingari, Alessandro Moretta, Lorenzo Moretta
Natural killer (NK) cells, the most important effectors of the innate lymphoid cells (ILCs), play a fundamental role in tumor immune-surveillance, defense against viruses and, in general, in innate immune responses. NK cell activation is mediated by several activating receptors and co-receptors able to recognize ligands on virus-infected or tumor cells. To prevent healthy cells from auto-aggression, NK cells are provided with strong inhibitory receptors (KIRs and NKG2A) which recognize HLA class I molecules on target cells and, sensing their level of expression, allow killing of targets underexpressing HLA-class I...
March 2017: Cytometry. Part B, Clinical Cytometry
https://www.readbyqxmd.com/read/28038471/prognostic-impact-of-immune-microenvironment-in-laryngeal-and-pharyngeal-squamous-cell-carcinoma-immune-cell-subtypes-immuno-suppressive-pathways-and-clinicopathologic-characteristics
#18
Georgia Karpathiou, Francois Casteillo, Jean-Baptiste Giroult, Fabien Forest, Pierre Fournel, Alessandra Monaya, Marios Froudarakis, Jean Marc Dumollard, Jean Michel Prades, Michel Peoc'h
BACKGROUND: Immune system affects prognosis of various malignancies. Anti-immune pathways like PD-L1 and CTLA4 are used by the tumor to overcome immune system and they serve as immunotherapy targets. The immune microenvironment of head-and-neck squamous cell carcinoma (SCCHN) has not been sufficiently studied. PATIENTS AND METHODS: 152 SCCHN were immunohistochemically studied for the expression of CD3, CD8, CD57, CD4, granzyme b, CD20, CD163, S100, PD-L1, CTLA4 and CXCR4...
December 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/27997006/-nivolumab-in-second-line-treatment-of-squamous-non-small-cell-lung-cancer
#19
Filippo De Marinis, Antonio Passaro
The treatment of non-small cell lung cancer (NSCLC) is changing dramatically in the last period, considering both non-squamous and squamous disease. In the last five years, the identification of different molecular predictive biomarker (e.g., EGFR, ALK e ROS1) and the utilize of new chemotherapy agents associated or not with antiangiogenics agents (e.g., bevacizumab and nintedanib), allowed the improvement of survival and related responses to these treatments. However, these advances, did not allow an improvement of the same endpoints in the management of NSCLC with squamous cell histology (SCC), where until very recently, docetaxel in monotherapy remained as a corner stone treatment for the second line, although associated with an unfavorable toxicity profile...
December 2016: Recenti Progressi in Medicina
https://www.readbyqxmd.com/read/27966264/pd1-and-pdl1-expression-in-primary-central-nervous-system-diffuse-large-b-cell-lymphoma-are-frequent-and-expression-of-pd1-predicts-poor-survival
#20
Marion Four, Valère Cacheux, Ariane Tempier, Dolorès Platero, Michel Fabbro, Grégory Marin, Nicolas Leventoux, Valérie Rigau, Valérie Costes-Martineau, Vanessa Szablewski
Primary central nervous system diffuse large B-cell lymphoma (PCNS-DLBCL) is a rare and aggressive type of diffuse large B-cell lymphoma (DLBCL) whit poorly understood pathogenesis. Finding biomarkers associated with patient survival may be important for understanding its physiopathology and to develop new therapeutic approaches. We investigated 32 PCNS-DLBCL from immunocompetent patients for BCL2, CMYC, LMO2, and P53 expression and for cytogenetic aberrations of BCL2, BCL6, and MYC genes, all known for their prognostic value in systemic DLBCL (s-DLBCL)...
December 13, 2016: Hematological Oncology
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