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Tumor immunology

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https://www.readbyqxmd.com/read/28344870/immunological-profiling-of-molecularly-classified-high-risk-endometrial-cancers-identifies-pole-mutant-and-microsatellite-unstable-carcinomas-as-candidates-for-checkpoint-inhibition
#1
Florine A Eggink, Inge C Van Gool, Alexandra Leary, Pamela M Pollock, Emma J Crosbie, Linda Mileshkin, Ekaterina S Jordanova, Julien Adam, Luke Freeman-Mills, David N Church, Carien L Creutzberg, Marco De Bruyn, Hans W Nijman, Tjalling Bosse
High-risk endometrial cancer (EC) is an aggressive disease for which new therapeutic options are needed. Aims of this study were to validate the enhanced immune response in highly mutated ECs and to explore immune profiles in other EC subgroups. We evaluated immune infiltration in 116 high-risk ECs from the TransPORTEC consortium, previously classified into four molecular subtypes: (i) ultramutated POLE exonuclease domain-mutant ECs (POLE-mutant); (ii) hypermutated microsatellite unstable (MSI); (iii) p53-mutant; and (iv) no specific molecular profile (NSMP)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344868/langerhans-cells-and-nk-cells-cooperate-in-the-inhibition-of-chemical-skin-carcinogenesis
#2
Daniela Ortner, Christoph H Tripp, Kerstin Komenda, Sandrine Dubrac, Bernhard Zelger, Martin Hermann, Wolfgang Doppler, Piotr Z Tymoszuk, Louis Boon, Björn E Clausen, Patrizia Stoitzner
Tissue immunosurveillance is an important mechanism to prevent cancer. Skin treatment with the carcinogen 7,12-dimethylbenz(a)anthracene (DMBA), followed by the tumor promoter 12-O-tetra-decanoyl-phorbol-13-acetate (TPA), is an established murine model for squamous cell carcinoma (SCC). However, the innate immunological events occurring during the initiation of chemical carcinogenesis with DMBA remain elusive. Here, we discovered that natural killer (NK) cells and Langerhans cells (LC) cooperate to impair this oncogenic process in murine skin...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344805/utilization-of-cholera-toxin-b-as-a-mucosal-adjuvant-elicits-antibody-mediated-protection-against-s-pneumoniae-infection-in-mice
#3
Kari Wiedinger, Daniel Pinho, Constantine Bitsaktsis
BACKGOUND: The introduction of the pneumococcal conjugate and polysaccharide vaccines have been valuable tools for combating invasive pneumococcal infection in children and healthy adults. Despite the available vaccination strategies, pneumococcal pneumonia and associated diseases continue to cause substantial morbidity and mortality, particularly in individuals with chronic disease and ageing populations. Next-generation pneumococcal vaccines will need to be highly immunogenic across patient populations providing both mucosal and systemic protective immunity...
February 2017: Therapeutic Advances in Vaccines
https://www.readbyqxmd.com/read/28343731/endoplasmic-reticulum-aminopeptidase-2-a-common-immunological-link-to-adverse-pregnancy-outcomes-and-cancer-clearance
#4
Eun D Lee
Endoplasmic Reticulum Aminopeptidase 2 (ERAP2) trims HLA class I-binding peptides, determining the peptide repertoire presented for immune recognition. Variation in the ERAP2 amino acid sequence could affect the ability of some fetuses and tumors to achieve immune evasion. For example, homozygosity for an ERAP2 variant that has increased trimming efficiency for hydrophobic molecules has never been detected in mothers and fetuses. Thus, it is possible that this single nucleotide polymorphism (SNP) in the ERAP2 gene has been selected against in order to prevent alteration of the immune privileged uterine environment, and to allow tumors to escape immune recognition...
March 18, 2017: Placenta
https://www.readbyqxmd.com/read/28338506/a-preliminary-report-radical-surgery-and-stem-cell-transplantation-for-the-treatment-of-patients-with-pancreatic-cancer
#5
Brigitta Omazic, Burcu Ayoglu, Matthias Löhr, Ralf Segersvärd, Caroline Verbeke, Isabelle Magalhaes, Zuzana Potacova, Jonas Mattsson, Alexei Terman, Sam Ghazi, Nils Albiin, Nikolaos Kartalis, Peter Nilsson, Thomas Poiret, Liu Zhenjiang, Rainer Heuchel, Jochen M Schwenk, Johan Permert, Markus J Maeurer, Olle Ringden
We examined the immunologic effects of allogeneic hematopoietic stem cell transplantation (HSCT) in the treatment of pancreatic ductal adenocarcinoma, a deadly disease with a median survival of 24 months for resected tumors and a 5-year survival rate of 6%. After adjuvant chemotherapy, 2 patients with resected pancreatic ductal adenocarcinoma underwent HSCT with HLA-identical sibling donors. Comparable patients who underwent radical surgery, but did not have a donor, served as controls (n=6). Both patients developed humoral and cellular (ie, HLA-A*01:01-restricted) immune responses directed against 2 novel tumor-associated antigens (TAAs), INO80E and UCLH3 after HSCT...
March 23, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28337274/decitabine-treatment-sensitizes-tumor-cells-to-t-cell-mediated-cytotoxicity-in-patients-with-myelodysplastic-syndromes
#6
Zheng Zhang, Qi He, Ying Tao, Juan Guo, Feng Xu, Ling-Yun Wu, You-Shan Zhao, Dong Wu, Li-Yu Zhou, Ji-Ying Su, Lu-Xi Song, Chao Xiao, Xiao Li, Chun-Kang Chang
Decitabine treatment improves immunological recognition that increases expression of cancer-testis antigens (CTAs) against solid tumors. The mechanisms of decitabine enhancement of immunogenicity when used for patients with myelodysplastic syndromes (MDS) remain unclear. In the present study, we found relatively low baseline expression of MAGE-A1, MAGE-A3, and SP17 in MDS-derived cell lines. Decitabine treatment significantly improved MAGE-A1, MAGE-A3, and SP17 expression in these cell lines and in MDS patients...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28332219/targeting-immunotherapy-to-the-tumor-microenvironment
#7
Michael Dougan, Stephanie K Dougan
Targeting drugs to the tumor microenvironment has long been appreciated as a means of increasing local concentrations and decreasing systemic toxicities. How drug targeting might apply to immune-based therapies is less clear. In this review, we explain the immunology of cancer, with a focus on the principles of in situ vaccination. Certain types of therapies are more amenable to local versus systemic delivery; these include cytokines, adjuvants, radiation, and agents targeting tumor-resident cell populations...
March 23, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28331999/the-acidic-microenvironment-as-a-possible-niche-of-dormant-tumor-cells
#8
REVIEW
Silvia Peppicelli, Elena Andreucci, Jessica Ruzzolini, Anna Laurenzana, Francesca Margheri, Gabriella Fibbi, Mario Del Rosso, Francesca Bianchini, Lido Calorini
Although surgical excision, chemo-, and radio-therapy are clearly advanced, tumors may relapse due to cells of the so-called "minimal residual disease". Indeed, small clusters of tumor cells persist in host tissues after treatment of the primary tumor elaborating strategies to survive and escape from immunological attacks before their relapse: this variable period of remission is known as "cancer dormancy". Therefore, it is crucial to understand and consider the major concepts addressing dormancy, to identify new targets and disclose potential clinical strategies...
March 22, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28331797/paradoxical-response-with-increased-tumor-necrosis-factor-%C3%AE-levels-to-anti-tuberculosis-treatment-in-a-patient-with-disseminated-tuberculosis
#9
Sho Watanabe, Yugo Kaneko, Hironori Kawamoto, Tomoki Maehara, Yuri Baba, Ikumi Fujisaki, Nayuta Saito, Kai Ryu, Aya Seki, Tsugumi Horikiri, Akira Kinoshita, Hiroshi Takeda, Keisuke Saito, Kazuyosi Kuwano
It has been reported that tuberculosis (TB) worsens after cessation of tumor necrosis factor-α inhibitors and starting anti-TB treatment. Little is known about the immunological pathogenesis of this paradoxical response (PR). We report the first case of a TB patient in whom PR occurred concurrently with elevation of circulating tumor necrosis factor-α (TNFα) levels. A 75-year-old woman, who had been treated with adalimumab for SAPHO syndrome, developed disseminated TB. Soon after administration of anti-TB treatment (isoniazid, rifampicin, pyrazinamide, and ethambutol), and after discontinuation of adalimumab, a PR occurred...
2017: Respiratory Medicine Case Reports
https://www.readbyqxmd.com/read/28325688/current-and-emerging-molecular-tests-for-human-papillomavirus-related-neoplasia-in-the-genomic-era
#10
REVIEW
Sixto M Leal, Margaret L Gulley
Laboratory tests have a key role in preventing human papillomavirus (HPV)-driven carcinomas and in guiding therapeutic interventions. An understanding of the virology, immunology, and carcinogenesis of HPV is essential for choosing appropriate diagnostic test modalities and developing new and even more effective cancer prevention strategies. HPV infects basal epithelial cells on multiple surfaces and induces carcinoma primarily in the cervix and the oropharynx. HPV types are stratified as high risk or low risk based on their carcinogenic potential, driven largely by viral interference with cell cycle regulation and the DNA damage response to promote continuous cell division while thwarting apoptosis, which enables mutation accumulation...
March 18, 2017: Journal of Molecular Diagnostics: JMD
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
#11
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/28325250/radiotherapy-in-the-age-of-cancer-immunology-current-concepts-and-future-developments
#12
REVIEW
Mauro Loi, Isacco Desideri, Daniela Greto, Monica Mangoni, Mariangela Sottili, Icro Meattini, Carlotta Becherini, Francesca Terziani, Camilla Delli Paoli, Emanuela Olmetto, Pierluigi Bonomo, Lorenzo Livi
Major advances in the knowledge of cancer biology and its interactions with tumor immune environment led to the emergence, in the last five years of new immunotherapy-based treatment strategies in cancer patients. At the same time, improvement in radiation technique and progress in radiobiology allowed in the last decade to expand the applications of radiotherapy in a growing number of settings. At present, there are strong theoretical basis to propose immune-enhanced radiation therapy that may represent in the future a new paradigm of treatment, combining the intrinsic power of radiotherapy to elicit a specific, systemic, tumor-directed immune response with modern highly conformal and precise dose delivery, in order to maximize response at the major site of disease and obtain durable disease control...
April 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28325210/breast-cancer-immunology-and-immunotherapy-current-status-and-future-perspectives
#13
L de la Cruz-Merino, M Chiesa, R Caballero, F Rojo, N Palazón, F H Carrasco, V Sánchez-Margalet
Cancer immunology has gained renewed interest in the past few years due to emerging findings on mechanisms involved in tumoral immune evasion. Indisputably, immune edition is currently considered a critical hallmark of cancer. Basic research has revealed new targets which can be modulated in the clinical setting with new compounds and strategies. As recent evidence confirms, breast cancer (BC) is a complex and heterogeneous disease in which host immune responses play a substantial role. T-infiltrating lymphocytes measurement is suggested as a powerful new tool necessary to predict early BC evolution, especially in HER2-positive and triple negative subtypes...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28323111/nanoparticles-for-tumor-immunotherapy
#14
REVIEW
Xinlong Zang, Xiuli Zhao, Haiyang Hu, Mingxi Qiao, Yihui Deng, Dawei Chen
Although most researches and therapies have been focused on the tumor itself, it is becoming clear that immune cells can not only suppress tumor development but support and maintain their malignant type. Promising recent developments in immunology will provide opportunities for tumor-specific immunotherapy, which can orchestrate the patients immune system to target, fight and eradicate cancer cells without destroying healthy cells. However, antitumor immunity driven by self-immune system alone may be therapeutically insufficient...
March 18, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28322382/regulation-of-raw-264-7-cell-mediated-immunity-by-polysaccharides-from-agaricus-blazei-murill-via-the-mapk-signal-transduction-pathway
#15
Feier Cheng, Xiaoyan Yan, Miaoqing Zhang, Mingchang Chang, Shaojun Yun, Junlong Meng, Jingyu Liu, Cui-Ping Feng
Agaricus blazei Murill (ABM) is a common anticancer folk remedy. Its active ingredients, i.e., polysaccharides, have been isolated and exhibit indirect tumor-suppressing activity via immunological activation. The effects of polysaccharides derived from A. blazei Murill (ABMP) on RAW 264.7 cells were examined by western blotting and real-time reverse transcription polymerase chain reaction (RT-PCR). The effects of 500, 1000, and 2000 μg mL(-1) ABMP on the growth of RAW 264.7 cells were evaluated by measuring the OD490 value; the optimum concentration was found to be 1000 μg mL(-1)...
March 21, 2017: Food & Function
https://www.readbyqxmd.com/read/28321810/overview-of-basic-immunology-for-clinical-investigators
#16
Bettzy Stephen, Joud Hajjar
Tumor exists as a complex network of structures with an ability to evolve and evade the host immune surveillance mechanism. The immune milieu which includes macrophages, dendritic cells, natural killer cells, neutrophils, mast cells, B cells, and T cells are found in the core, the invasive margin, or the adjacent stromal or lymphoid component of the tumor. The immune infiltrate is heterogeneous and varies within a patient and between patients of the same tumor histology. The location, density, functionality, and the cross talk between the immune cells in the tumor microenvironment influence the nature of immune response, prognosis, and treatment outcomes in cancer patients...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28321480/a-new-peptide-vaccine-ocv-501-in-vitro-pharmacology-and-phase-1-study-in-patients-with-acute-myeloid-leukemia
#17
Yukio Kobayashi, Toru Sakura, Shuichi Miyawaki, Kazuyuki Toga, Shinji Sogo, Yuji Heike
Wilms' tumor 1 (WT1) is a promising target of new immunotherapies for acute myeloid leukemia (AML) as well as for other cancers. OCV-501 is a helper peptide derived from the WT1 protein. OCV-501 induced OCV-501-specific Type 1 T-helper (Th1) responses dose-dependently and stimulated helper activity of the specific Th1 cells in peripheral blood mononuclear cells from healthy donors. OCV-501 also enhanced the increase in WT1-killer peptide-specific cytotoxic T lymphocytes. OCV-501 stimulated the OCV-501-specific Th1 clones in an HLA class-II restricted manner and formed a complex with HLA class-II protein...
March 20, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28321385/the-laparoscopically-harvested-omental-free-flap-a-compelling-option-for-craniofacial-and-cranial-base-reconstruction
#18
Peter D Costantino, David Shamouelian, Tristan Tham, Robert Andrews, Wojciech Dec
Background Management of craniofacial and cranial base tumors is a challenge due to the anatomic intricacies associated with the calvarium, the pathological diversity of lesions that present, and the potential complications. Clinical outcomes in laparoscopically harvested omentum free flaps for cranial base and craniofacial reconstruction are presented in this paper, in the largest case series to date. Methods A retrospective single-center experience for over 10 years with laparoscopically harvested omentum flaps used to reconstruct craniofacial and cranial base defects...
April 2017: Journal of Neurological Surgery. Part B, Skull Base
https://www.readbyqxmd.com/read/28321224/specific-igg-antibodies-react-to-mimotopes-of-bk-polyomavirus-a-small-dna-tumor-virus-in-healthy-adult-sera
#19
Silvia Pietrobon, Ilaria Bononi, Elisa Mazzoni, Francesca Lotito, Marco Manfrini, Andrea Puozzo, Federica Destro, Giovanni Guerra, Pier Francesco Nocini, Fernanda Martini, Mauro G Tognon
BK polyomavirus (BKPyV) was isolated in 1971 from the urine of a kidney transplant patient. Soon after its identification, BKPyV was characterized as a kidney-tropic virus, which is responsible of a significant fraction of the rejection of transplant kidney in the host. Moreover, in experimental conditions, BKPyV is able to transform different types of animal and human cells and to induce tumors of different histotypes in experimental animals. BKPyV DNA sequences have been detected in healthy individuals and cancer patients using polymerase chain reaction/Shouthern blot hybridization methods...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28320438/regulatory-t-cell-frequency-but-not-plasma-il-33-levels-represents-potential-immunological-biomarker-to-predict-clinical-response-to-intravenous-immunoglobulin-therapy
#20
Mohan S Maddur, Emmanuel Stephen-Victor, Mrinmoy Das, Praveen Prakhar, Varun K Sharma, Vikas Singh, Magalie Rabin, Jamma Trinath, Kithiganahalli N Balaji, Francis Bolgert, Jean-Michel Vallat, Laurent Magy, Srini V Kaveri, Jagadeesh Bayry
BACKGROUND: Intravenous immunoglobulin (IVIG) is a polyspecific pooled immunoglobulin G preparation and one of the commonly used therapeutics for autoimmune diseases including those of neurological origin. A recent report in murine model proposed that IVIG expands regulatory T (Treg) cells via induction of interleukin 33 (IL-33). However, translational insight on these observations is lacking. METHODS: Ten newly diagnosed Guillain-Barré syndrome (GBS) patients were treated with IVIG at the rate of 0...
March 20, 2017: Journal of Neuroinflammation
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