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https://www.readbyqxmd.com/read/29352713/clinical-variables-associated-with-overall-survival-in-metastatic-castration-resistant-prostate-cancer-patients-treated-with-sipuleucel-t-immunotherapy
#1
Xiao X Wei, Jaselle Perry, Emily Chang, Li Zhang, Robert A Hiatt, Charles J Ryan, Eric J Small, Lawrence Fong
BACKGROUND: Sipuleucel-T is an autologous cell-based cancer immunotherapy for men with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). Its approval by the Food and Drug Administration was based on demonstration of an overall survival (OS) benefit in randomized placebo-controlled phase III trials. However, treatment was associated with a prostate-specific antigen (PSA) decline in only a small minority of patients. Understanding the clinical factors that are associated with OS could help guide treatment decisions, including patient selection and the timing of sipuleucel-T relative to other therapies...
December 27, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/29348866/protein-methyltransferases-and-demethylases-dictate-cd8-t-cell-exclusion-in-squamous-cell-carcinoma-of-the-head-and-neck
#2
Theodore Vougiouklakis, Riyue Bao, Yusuke Nakamura, Vassiliki Saloura
A subset of patients with recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN) benefit from pembrolizumab and nivolumab, but the majority of patients do not probably due to lack of activated cytotoxic CD8+ T-cells in their tumor tissues. Herein, we aim to investigate whether specific protein methyltransferases (PMTs) and demethylases (PDMTs) could play any roles in the CD8+ T-cell exclusion process in HPV-negative SCCHN. RNA sequencing data from the TCGA database were interrogated for HPV-negative SCCHN patients using a 10-gene chemokine signature that classifies SCCHN tissues into CD8+ T-cell inflamed and non-CD8+ T-cell inflamed phenotypes...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348865/targeting-t-cell-malignancies-using-anti-cd4-car-nk-92-cells
#3
Kevin G Pinz, Elizabeth Yakaboski, Alexander Jares, Hua Liu, Amelia E Firor, Kevin H Chen, Masayuki Wada, Huda Salman, William Tse, Nabil Hagag, Fengshuo Lan, Elaine Lai-Han Leung, Xun Jiang, Yupo Ma
Peripheral T-cell lymphomas (PTCLs) are a group of very aggressive non-Hodgkin's lymphomas (NHLs) with poor prognoses and account for a majority of T-cell malignancies. Overall, the standard of care for patients with T-cell malignancies is poorly established, and there is an urgent clinical need for a new approach. As demonstrated in B-cell malignancies, chimeric antigen receptor (CAR) immunotherapy provides great hope as a curative treatment regimen. Because PTCLs develop from mature T-cells, these NHLs are commonly CD4+, and CD4 is highly and uniformly expressed...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348598/increased-diversity-with-reduced-diversity-evenness-of-tumor-infiltrating-t-cells-for-the-successful-cancer-immunotherapy
#4
Akihiro Hosoi, Kazuyoshi Takeda, Koji Nagaoka, Tamaki Iino, Hirokazu Matsushita, Satoshi Ueha, Shin Aoki, Kouji Matsushima, Masato Kubo, Teppei Morikawa, Kazutaka Kitaura, Ryuji Suzuki, Kazuhiro Kakimi
To facilitate the optimization of cancer immunotherapy lacking immune-related adverse events, we performed TCR repertoire analysis of tumor-infiltrating CD8+ T-cells in B16 melanoma-bearing mice receiving anti-PD-1, anti-CTLA-4, anti-4-1BB, anti-CD4 or a combination of anti-PD-1 and 4-1BB antibodies. Although CD8+ T-cells in the tumor were activated and expanded to a greater or lesser extent by these therapies, tumor growth suppression was achieved only by anti-PD-1, anti-PD-1/4-1BB combined, or by anti-CD4 treatment, but not by anti-CTLA-4 or anti-4-1BB monotherapy...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29348432/genome-wide-association-study-of-self-reported-food-reactions-in-japanese-identifies-shrimp-and-peach-specific-loci-in-the-hla-dr-dq-gene-region
#5
Seik-Soon Khor, Ryoko Morino, Kazuyuki Nakazono, Shigeo Kamitsuji, Masanori Akita, Maiko Kawajiri, Tatsuya Yamasaki, Azusa Kami, Yuria Hoshi, Asami Tada, Kenichi Ishikawa, Maaya Hine, Miki Kobayashi, Nami Kurume, Naoyuki Kamatani, Katsushi Tokunaga, Todd A Johnson
Food allergy is an increasingly important health problem in the world. Several genome-wide association studies (GWAS) focused on European ancestry samples have identified food allergy-specific loci in the HLA class II region. We conducted GWAS of self-reported reactivity with common foods using the data from 11011 Japanese women and identified shrimp and peach allergy-specific loci in the HLA-DR/DQ gene region tagged by rs74995702 (P = 6.30 × 10-17, OR = 1.91) and rs28359884 (P = 2.3 × 10-12, OR = 1...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29346301/braf-and-mek-inhibitors-influence-the-function-of-reprogrammed-t-cells-consequences-for-adoptive-t-cell-therapy
#6
Jan Dörrie, Lek Babalija, Stefanie Hoyer, Kerstin F Gerer, Gerold Schuler, Lucie Heinzerling, Niels Schaft
BRAF and MEK inhibitors (BRAFi/MEKi), the standard treatment for patients with BRAFV600 mutated melanoma, are currently explored in combination with various immunotherapies, notably checkpoint inhibitors and adoptive transfer of receptor-transfected T cells. Since two BRAFi/MEKi combinations with similar efficacy are approved, potential differences in their effects on immune cells would enable a rational choice for triple therapies. Therefore, we characterized the influence of the clinically approved BRAFi/MEKi combinations dabrafenib (Dabra) and trametinib (Tram) vs...
January 18, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29346180/development-of-a-pd-l1-complementary-diagnostic-immunohistochemistry-assay-sp142-for-atezolizumab
#7
Bharathi Vennapusa, Brian Baker, Marcin Kowanetz, Jennifer Boone, Ina Menzl, Jean-Marie Bruey, Gregg Fine, Sanjeev Mariathasan, Ian McCaffery, Simonetta Mocci, Sandra Rost, Dustin Smith, Eslie Dennis, Szu-Yu Tang, Bita Damadzadeh, Espen Walker, Priti S Hegde, J Andrew Williams, Hartmut Koeppen, Zachary Boyd
Cancer immunotherapies, such as atezolizumab, are proving to be a valuable therapeutic strategy across indications, including non-small cell lung cancer (NSCLC) and urothelial cancer (UC). Here, we describe a diagnostic assay that measures programmed-death ligand 1 (PD-L1) expression, via immunohistochemistry, to identify patients who will derive the most benefit from treatment with atezolizumab, a humanized monoclonal anti-PD-L1 antibody. We describe the performance of the VENTANA PD-L1 (SP142) Assay in terms of specificity, sensitivity, and the ability to stain both tumor cells (TC) and tumor-infiltrating immune cells (IC), in NSCLC and UC tissues...
January 16, 2018: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/29345636/promoting-the-accumulation-of-tumor-specific-t-cells-in-tumor-tissues-by-dendritic-cell-vaccines-and-chemokine-modulating-agents
#8
Nataša Obermajer, Julie Urban, Eva Wieckowski, Ravikumar Muthuswamy, Roshni Ravindranathan, David L Bartlett, Pawel Kalinski
This protocol describes how to induce large numbers of tumor-specific cytotoxic T cells (CTLs) in the spleens and lymph nodes of mice receiving dendritic cell (DC) vaccines and how to modulate tumor microenvironments (TMEs) to ensure effective homing of the vaccination-induced CTLs to tumor tissues. We also describe how to evaluate the numbers of tumor-specific CTLs within tumors. The protocol contains detailed information describing how to generate a specialized DC vaccine with augmented ability to induce tumor-specific CTLs...
February 2018: Nature Protocols
https://www.readbyqxmd.com/read/29345001/wheat-oral-immunotherapy-was-moderately-successful-but-was-associated-with-very-frequent-adverse-events-in-children-aged-6-18-years
#9
Petri Kulmala, Anna S Pelkonen, Mikael Kuitunen, Marita Paassilta, Sami Remes, Rüdiger Schultz, Teija Dunder, Sami Turunen, Mika J Mäkelä
AIM: This study investigated oral immunotherapy for children aged 6-18 years with wheat allergies. METHODS: Well-cooked wheat spaghetti was given to 100 children with wheat allergies every day for 17 weeks, increasing from 0.3mg to 2,000mg of wheat protein, followed by three-month and nine-month maintenance phases. Blood samples were taken before therapy and at follow-up visits. The study was carried out in 2009-2015 in four Finnish paediatric allergology units...
January 18, 2018: Acta Paediatrica
https://www.readbyqxmd.com/read/29344404/unleashing-the-tiger-iatrogenic-autoimmunity-from-cancer-immunotherapy-drugs
#10
Queenie Luu, Gabor Major
Immune checkpoint inhibitors can lead to the development of organ and non-organ specific immune related adverse events.
January 2018: JRSM Open
https://www.readbyqxmd.com/read/29344312/an-endogenous-vaccine-based-on-fluorophores-and-multivalent-immunoadjuvants-regulates-tumor-micro-environment-for-synergistic-photothermal-and-immunotherapy
#11
Ling Li, Suleixin Yang, Linjiang Song, Yan Zeng, Tao He, Ning Wang, Chuan Yu, Tao Yin, Li Liu, Xiawei Wei, Qinjie Wu, Yuquan Wei, Li Yang, Changyang Gong
Recently, near-infrared (NIR) light-based photothermal therapy (PTT) has been widely applied in cancer treatment. However, in most cases, the tissue penetration depth of NIR light is not sufficient and thus photothermal therapy is unable to completely eradicate deep, seated tumors inevitably leading to recurrence of the tumor. Due to this significant limitation of NIR, improved therapeutic strategies are urgently needed. Methods: We developed an endogenous vaccine based on a novel nanoparticle platform for combinatorial photothermal ablation and immunotherapy...
2018: Theranostics
https://www.readbyqxmd.com/read/29343286/diagnosis-and-management-of-transthyretin-familial-amyloid-polyneuropathy-in-japan-red-flag-symptom-clusters-and-treatment-algorithm
#12
REVIEW
Yoshiki Sekijima, Mitsuharu Ueda, Haruki Koike, Sonoko Misawa, Tomonori Ishii, Yukio Ando
Hereditary ATTR (ATTRm) amyloidosis (also called transthyretin-type familial amyloid polyneuropathy [ATTR-FAP]) is an autosomal-dominant, adult-onset, rare systemic disorder predominantly characterized by irreversible, progressive, and persistent peripheral nerve damage. TTR gene mutations (e.g. replacement of valine with methionine at position 30 [Val30Met (p.Val50Met)]) lead to destabilization and dissociation of TTR tetramers into variant TTR monomers, which form amyloid fibrils that deposit in peripheral nerves and various organs, giving rise to peripheral and autonomic neuropathy and several non-disease specific symptoms...
January 17, 2018: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/29343281/p-mapa-immunotherapy-potentiates-the-effect-of-cisplatin-on-serous-ovarian-carcinoma-through-targeting-tlr4-signaling
#13
Luiz Gustavo de Almeida Chuffa, Grazielle de Moura Ferreira, Luiz Antonio Lupi, Iseu da Silva Nunes, Wagner José Fávaro
BACKGROUND: Toll-like receptors (TLRs) are transmembrane proteins expressed on the surface of ovarian cancer (OC) and immune cells. Identifying the specific roles of the TLR-mediated signaling pathways in OC cells is important to guide new treatments. Because immunotherapies have emerged as the adjuvant treatment for patients with OC, we investigated the effect of a promising immunotherapeutic strategy based on protein aggregate magnesium-ammonium phospholinoleate-palmitoleate anhydride (P-MAPA) combined with cisplatin (CIS) on the TLR2 and TLR4 signaling pathways via myeloid differentiation factor 88 (MyD88) and TLR-associated activator of interferon (TRIF) in an in vivo model of OC...
January 17, 2018: Journal of Ovarian Research
https://www.readbyqxmd.com/read/29342409/development-and-characterization-of-an-allergoid-of-cat-dander-for-immunotherapy
#14
J P Sola, Y Pedreño, A Cerezo, M Peñalver-Mellado
BACKGROUND: Allergy to cats is a frequent cause of sensitization to indoor allergens and currently there are few alternatives to specific immunotherapy with cat native extracts. The objective is to develop and characterize a new allergoid to increase the tools available for use in clinical practice. METHODS: The allergoid cat dander extract (ACD) was developed from a native cat dander extract (NCD) by modification with glutaraldehyde, and the optimal process control was determined by SDS-PAGE, DOT BLOT and determination of free amine groups...
January 13, 2018: Allergologia et Immunopathologia
https://www.readbyqxmd.com/read/29340620/delivery-of-tapasin-modified-ctl-epitope-peptide-via-cytoplasmic-transduction-peptide-induces-ctls-by-jak-stat-signaling-pathway-in-vivo
#15
Shanshan Wu, Xiaohua Chen, Yuyan Tang, Yi Zhang, Dan Li, Jie Chen, Jieling Wang, Zhenghao Tang, Guoqing Zang, Yongsheng Yu
Hepatitis B virus (HBV)-specific cytotoxic T lymphocytes (CTLs) play a vital role in viral control and clearance. Recent studies have elucidated that Tapasin, an endoplasmic reticulum chaperone, is a well-known molecule that appears to be essential in peptide-loading process. The Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway plays an important role in immune response regulation and cytokines secretion. We have previously verified that fusion protein CTP-HBcAg18-27-Tapasin could facilitate the maturation of bone marrow derived dendritic cells and enhance specific CTLs responses in vitro, which might be associated with the activation of JAK/STAT signaling pathway...
January 11, 2018: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/29340102/the-impact-of-antibiotic-usage-on-the-efficacy-of-chemoimmunotherapy-is-contingent-on-the-source-of-tumor-reactive-t-cells
#16
Michal P Kuczma, Zhi-Chun Ding, Tao Li, Tsadik Habtetsion, Tingting Chen, Zhonglin Hao, Locke Bryan, Nagendra Singh, James N Kochenderfer, Gang Zhou
In recent years the combined use of chemotherapy and immunotherapy, collectively termed chemoimmunotherapy, has emerged as a promising treatment option for patients with cancer. Antibiotics are commonly used to reduce infection-related complications in patients undergoing chemotherapy. Intriguingly, accumulating evidence has implicated gut microbiota as a critical determinant of host antitumor immune responses, raising the question as to whether the use of broad-spectrum antibiotics would invariably diminish tumor response to chemoimmunotherapies...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29339650/oral-immunotherapy-in-japanese-children-with-anaphylactic-peanut-allergy
#17
Ken-Ichi Nagakura, Sakura Sato, Noriyuki Yanagida, Makoto Nishino, Tomoyuki Asaumi, Kiyotake Ogura, Motohiro Ebisawa
BACKGROUND: Reports on oral immunotherapy (OIT) for anaphylactic food allergy are lacking. We investigated the efficacy and safety of peanut OIT for anaphylactic patients. METHODS: We enrolled 22 peanut anaphylactic patients who underwent OIT between 2011 and 2013, all of whom demonstrated anaphylaxis during a baseline double-blind, placebo-controlled food challenge. After starting in-hospital OIT, participants gradually increased ingestion to 795 mg of peanut protein per day at home and then took a maintenance dose (795 mg) daily...
January 16, 2018: International Archives of Allergy and Immunology
https://www.readbyqxmd.com/read/29339209/extratumoral-pd-1-blockade-does-not-perpetuate-obesity-associated-inflammation-in-esophageal-adenocarcinoma
#18
Karen C Galvin, Melissa J Conroy, Suzanne L Doyle, Margaret R Dunne, Ronan Fahey, Emma Foley, Katie E O'Sullivan, Derek G Doherty, Justin G Geoghegan, Narayanasamy Ravi, Cliona O'Farrelly, John V Reynolds, Joanne Lysaght
Checkpoint inhibitors, such as anti-PD-1 (Programmed death-1), are transforming cancer treatment for inoperable or advanced disease. As the incidence of obesity-associated malignancies, including esophageal adenocarcinoma (EAC) continue to increase and treatment with checkpoint inhibitors are being FDA approved for a broader range of cancers, it is important to assess how anti-PD-1 treatment might exacerbate pre-existing inflammatory processes at other sites. Outside the EAC tumor, the omentum and liver were found to be enriched with substantial populations of PD-1 expressing T cells...
January 12, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29338609/chemotherapy-induced-immunomodulation-in-non-small-cell-lung-cancer-a-rationale-for-combination-chemoimmunotherapy
#19
Hua Zheng, Masha Zeltsman, Marjorie G Zauderer, Takashi Eguchi, Raj G Vaghjiani, Prasad S Adusumilli
Spurred by the survival benefits seen with the use of checkpoint blockade in non-small-cell lung cancer (NSCLC), there has been a growing interest in the potential applications of immunotherapy. Despite this, the objective response rate for single-agent immunotherapy remains ≤20% in patients with advanced NSCLC. A combinatorial approach that utilizes both chemotherapy and immunotherapy is a potential strategy to increase antitumor efficacy. Accumulating evidence has shown that the immunomodulatory effects of chemotherapeutic agents can be exploited in a combinational approach...
September 2017: Immunotherapy
https://www.readbyqxmd.com/read/29337913/proteomic-analysis-and-identification-of-possible-allergenic-proteins-in-mature-pollen-of-populus-tomentosa
#20
Liuqiang Wang, Xiaoling Zhang, Jin Zhang, Wei Fan, Mengzhu Lu, Jianjun Hu
Pollen grains from Populus tomentosa, a widely cultivated tree in northern area of China, are considered to be an important aeroallergen causing severe allergic diseases. To gain insight into their allergenic components, mature Populus tomentosa pollen proteins were analyzed by two-dimensional gel electrophoresis (2-DE) and matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF/TOF MS). A total of 412 spots from mature pollen were resolved on pH 4-7 immobilized pH gradient (IPG) strips and 159 distinct proteins were identified from 242 spots analyzed...
January 16, 2018: International Journal of Molecular Sciences
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