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https://www.readbyqxmd.com/read/28077434/transfer-of-allogeneic-cd4-t-cells-rescues-cd8-t-cells-in-anti-pd-l1-resistant-tumors-leading-to-tumor-eradication
#1
Ainhoa Arina, Theodore G Karrison, Eva Galka, Karin Schreiber, Ralph R Weichselbaum, Hans Schreiber
Adoptively transferred CD8(+) T cells can stabilize the size of solid tumors over long periods of time by exclusively recognizing antigen cross-presented on tumor stroma. However, these tumors eventually escape T cell-mediated growth control. The aim of this study was to eradicate such persistent cancers. In our model, the SIYRYYGL antigen is expressed by cancer cells that lack the MHC-I molecule K(b) needed for direct presentation, but the antigen is picked up and cross-presented by tumor stroma. A single injection of antigen-specific 2C CD8(+) T cells caused long-term inhibition of tumor growth, but without further intervention, tumors started to progress after approximately 3 months...
January 11, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28062115/genotype-matched-treatment-for-patients-with-advanced-type-i-epithelial-ovarian-cancer-eoc
#2
A Spreafico, A M Oza, B A Clarke, H J Mackay, P Shaw, M Butler, N C Dhani, S Lheureux, M K Wilson, S Welch, T Zhang, C Yu, T Stockley, L L Siu, S Kamel-Reid, P L Bedard
BACKGROUND: Genomic alterations that activate the MAPK signaling pathway frequently occur in Type I Epithelial Ovarian Cancers (EOCs). We evaluated therapeutic response outcomes in patients with type I EOC treated with genotype-matched therapy on clinical trials enrolled in a prospective molecular profiling program. MATERIAL AND METHODS: Formalin fixed paraffin embedded tumor tissues were prospectively screened for genomic alterations using MALDI-ToF mass-spectrometry platform or targeted sequencing using the Illumina MiSeq TruSeq Amplicon Cancer Panel...
January 3, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28056322/-the-therapeutic-value-and-safety-of-icotinib-as-first-line-therapy-for-advanced-non-small-cell-lung-cancer-patients
#3
H Chen, H P Wang, L Zhang, X Y Si
Objective: To evaluate the safety and efficacy of icotinib as first-line therapy in Chinese non-small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) sensitive mutations. Methods: Patients with stage ⅢB/Ⅳ NSCLC who had EGFR sensitive mutation and had no previous treatment were enrolled into this study. The response rates, progress free survival (PFS), overall survival (OS), and the safety were analyzed. Results: Ninety advanced adenocarcinoma patients were enrolled in this study, 44 patients had partial response (PR), 42 patients had stable disease (SD), 4 patients had progressive disease (PD), with an overall response rate (ORR) of 48...
January 1, 2017: Zhonghua Nei Ke za Zhi [Chinese Journal of Internal Medicine]
https://www.readbyqxmd.com/read/28056053/soluble-b-and-t-lymphocyte-attenuator-correlates-to-disease-severity-in-sepsis-and-high-levels-are-associated-with-an-increased-risk-of-mortality
#4
Anna Lange, Jonas Sundén-Cullberg, Anders Magnuson, Olof Hultgren
INTRODUCTION AND AIMS: B- and T-lymphocyte Attenuator (BTLA), Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and Programmed Death 1 (PD-1) are co-inhibitory receptors that regulate T cell activation. In the present study of ICU-treated patients we measured plasma concentrations of their soluble isoforms, with the aim to evaluate their potential as sepsis biomarkers and utility as prognostic indicators. METHODS: 101 patients with sepsis, 28 patients with non-infectious critical illness (ICU controls) and 31 blood donors (healthy controls, HC) were included in the study...
2017: PloS One
https://www.readbyqxmd.com/read/28049139/a-randomized-phase-2-study-of-mk-2206-versus-everolimus-in-refractory-renal-cell-carcinoma
#5
E Jonasch, E Hasanov, P Corn, T Moss, K Shaw, S Stovall, V Marcott, B Gan, S Bird, X Wang, K Do, P Altamirano, A Zurita, L Doyle, P Lara, N M Tannir
BACKGROUND: Activation of the phosphoinisitide-3 kinase (PI3K) pathway through mutation and constitutive upregulation have been described in renal cell carcinoma (RCC), making it an attractive target for therapeutic intervention. We performed a randomized phase II study in vascular endothelial growth factor (VEGF) therapy refractory patients to determine whether MK-2206, an allosteric inhibitor of AKT, was more efficacious than the mammalian target of rapamycin inhibitor everolimus. PATIENTS AND METHODS: A total of 43 patients were randomized in a 2:1 distribution, with 29 patients assigned to the MK-2206 arm and 14 to the everolimus arm...
January 3, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28042144/novel-bet-protein-proteolysis-targeting-chimera-bet-protac-exerts-superior-lethal-activity-than-bromodomain-inhibitor-beti-against-post-myeloproliferative-neoplasm-mpn-secondary-s-aml-cells
#6
D T Saenz, W Fiskus, Y Qian, T Manshouri, K Rajapakshe, K Raina, K G Coleman, A P Crew, A Shen, C P Mill, B Sun, P Qiu, T M Kadia, N Pemmaraju, C DiNardo, M-S Kim, A J Nowak, C Coarfa, C M Crews, S Verstovsek, K N Bhalla
The PROTAC (proteolysis-targeting chimera) ARV-825 recruits bromodomain and extraterminal (BET) proteins to the E3 ubiquitin ligase cereblon, leading to degradation of BET proteins, including BRD4. Whereas the BET-protein inhibitor (BETi) OTX015 caused accumulation of BRD4, treatment with equimolar concentrations of ARV-825 caused sustained and profound depletion (>90%) of BRD4 and induced significantly more apoptosis in cultured and patient-derived (PD) CD34+ post-MPN sAML cells, while relatively sparing the CD34+ normal hematopoietic progenitor cells...
January 2, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28038394/increased-il-35-producing-tregs-and-cd19-il-35-cells-are-associated-with-disease-progression-in-leprosy-patients
#7
Mohd Tarique, Chaman Saini, Raza Ali Naqvi, Neena Khanna, D N Rao
BACKGROUND: The clinical forms of leprosy consist of a spectrum that reflects the host's immune response to the M. leprae; it provides an ideal model to study the host pathogen interaction and immunological dysregulation in humans. IL-10 and TGF-β producing Tregs are high in leprosy patients and responsible for immune suppression and M. leprae specific T cells anergy. In leprosy, involvement of IL-35 producing Tregs and Bregs remain unstudied. OBJECTIVE: To study the role of IL-35 producing Tregs and Bregs in the human leprosy...
December 27, 2016: Cytokine
https://www.readbyqxmd.com/read/28036275/lymphocyte-to-monocyte-ratio-is-associated-with-prognosis-of-diffuse-large-b-cell-lymphoma-correlation-with-cd163-positive-m2-type-tumor-associated-macrophages-not-pd-1-positive-tumor-infiltrating-lymphocytes
#8
Jingxuan Wang, Kun Gao, Wanting Lei, Lina Dong, Qijia Xuan, Meiyan Feng, Jinlu Wang, Xiangnan Ye, Tuan Jin, Zhongbai Zhang, Qingyuan Zhang
The research aims to examine the prognostic value of the lymphocyte-to-monocyte ratio (LMR), neutrophil-to- lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in diffuse large B-cell lymphoma (DLBCL). The relation of these hematologic indicators to poor antitumor immunity and prognosis must be investigated. Clinicopathologic data and survival information of 355 patients with DLBCL was retrospectively analyzed. Univariate analysis revealed that lower LMR (<2.71), higher NLR (≥2.81), CD163+ M2 tumor-associated macrophages (TAM) content ≥9...
December 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/28033288/immune-checkpoint-proteins-pd-1-and-tim-3-are-both-highly-expressed-in-liver-tissues-and-correlate-with-their-gene-polymorphisms-in-patients-with-hbv-related-hepatocellular-carcinoma
#9
Zhu Li, Na Li, Fang Li, Zhihua Zhou, Jiao Sang, Yanping Chen, Qunying Han, Yi Lv, Zhengwen Liu
Immune checkpoint proteins programmed death-1 (PD-1) and T-cell immunoglobulin domain and mucin domain containing molecule-3 (TIM-3) expression and their gene polymorphisms have separately been shown to be associated with hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC). This study simultaneously examined PD-1 and TIM-3 expression in liver tissues and PD1 and TIM3 polymorphisms and analyzed their correlations in 171 patients with HBV-related HCC and 34 patients with HBV-related cirrhosis...
December 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28031159/evolution-of-neoantigen-landscape-during-immune-checkpoint-blockade-in-non-small-cell-lung-cancer
#10
Valsamo Anagnostou, Kellie N Smith, Patrick M Forde, Noushin Niknafs, Rohit Bhattacharya, James White, Theresa Zhang, Vilmos Adleff, Jillian Phallen, Neha Wali, Carolyn Hruban, Violeta B Guthrie, Kristen Rodgers, Jarushka Naidoo, Hyunseok Kang, William H Sharfman, Christos Georgiades, Franco Verde, Peter Illei, Qing Kay Li, Edward Gabrielson, Malcolm V Brock, Cynthia A Zahnow, Stephen B Baylin, Robert Scharpf, Julie R Brahmer, Rachel Karchin, Drew M Pardoll, Victor E Velculescu
Immune checkpoint inhibitors have shown significant therapeutic responses against tumors containing increased mutation-associated neoantigen load. We have examined the evolving landscape of tumor neoantigens during the emergence of acquired resistance in non-small cell lung cancer patients after initial response to immune checkpoint blockade with anti-PD1 or anti-PD-1/anti-CTLA4 antibodies. Analyses of matched pretreatment and resistant tumors identified genomic changes resulting in loss of 7 to 18 putative mutation-associated neoantigens in resistant clones...
December 28, 2016: Cancer Discovery
https://www.readbyqxmd.com/read/28012568/improved-survival-after-induction-of-sepsis-by-cecal-slurry-in-pd-1-knockout-murine-neonates
#11
Whitney A Young, Eleanor A Fallon, Daithi S Heffernan, Philip A Efron, William G Cioffi, Alfred Ayala
BACKGROUND: Sepsis and the ensuing immune dysfunction continue to be major contributors to neonatal morbidity and mortality. Neonatal sepsis also is associated with profound immune dysfunction. We have recently identified a role for a family of coinhibitory molecules that are altered in murine sepsis and in critically ill adult patients, which may be a target for development of novel therapies. There is, however, a paucity of data pertaining to the role of coinhibitory checkpoint proteins in the control and modulation of neonatal sepsis...
December 21, 2016: Surgery
https://www.readbyqxmd.com/read/28007776/immune-cytolytic-activity-stratifies-molecular-subsets-of-human-pancreatic-cancer
#12
David Balli, Andrew J Rech, Ben Z Stanger, Robert H Vonderheide
PURPOSE: Immunotherapy has the potential to improve the dismal prognosis in pancreatic ductal adenocarcinoma (PDA), but clinical trials - including those with single-agent PD-1/PD-L1 inhibition - have been disappointing. Our aim was to examine the immune landscape of PDA as it relates to aspects of tumor biology, including neoepitope burden. EXPERIMENTAL DESIGN: We used publically available expression data from 134 primary resection PDA samples from The Cancer Genome Atlas to stratify patients according to a cytolytic T-cell activity expression index...
December 22, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28005469/clinical-significance-of-dynamics-of-programmed-death-ligand-1-expression-on-circulating-cd14-monocytes-and-cd19-b-cells-with-the-progression-of-hepatitis-b-virus-infection
#13
Zi-Yi Huang, Ping Xu, Jian-Hua Li, Chen-Hua Zeng, Hua-Feng Song, Hui Chen, Yi-Bei Zhu, Ying-Ying Song, Han-Lin Lu, Chun-Ping Shen, Xue-Guang Zhang, Mei-Ying Wu, Xue-Feng Wang
Programmed death-1 (PD-1) expression has been revealed to be upregulated on T cells and contributes to T cell exhaustion in patients with hepatitis B virus (HBV) infection. In this study, we investigated the dynamic expression of programmed death ligand-1 (PD-L1), the ligand of PD-1, on circulating CD14(+) monocytes and CD19(+) B cells of HBV-infected patients at the stages of chronic HBV (CHB) infection, liver cirrhosis (LC), and hepatocellular carcinoma (HCC), respectively. The results showed that compared with healthy controls, the levels of PD-L1 expression on CD14(+) and CD19(+) populations were both upregulated in CHB, LC, and HCC groups...
December 22, 2016: Viral Immunology
https://www.readbyqxmd.com/read/27999289/characterization-of-the-microenvironment-of-nodular-lymphocyte-predominant-hodgkin-lymphoma
#14
Lydia Visser, Rui Wu, Bea Rutgers, Arjan Diepstra, Anke van den Berg
Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is characterized by a low percentage of neoplastic lymphocyte predominant (LP) cells in a background of lymphocytes. The goal of this study is to characterize the microenvironment in NLPHL. Ten NLPHL cases and seven reactive lymph nodes (RLN) were analyzed by flow cytometry for the main immune cells and multiple specific subpopulations. To discriminate between cells in or outside the tumor cell area, we used CD26. We observed significantly lower levels of CD20+ B-cells and CD56+ NK cells and higher levels of CD4+ T-cells in NLPHL in comparison to RLN...
December 16, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27992987/-cytotoxic-effect-of-palladium-ii-inclusion-compounds-in-beta-cyclodextrin
#15
Nancy Jaimes, Siham Salmen, Melisa Carolina Colmenares, Ana Esperanza Burgos, Lenka Tamayo, Rosa Virginia Mendoza, Astrid Cantor
INTRODUCTION: Thiosemicarbazones and palladium (II) complexes have antineoplastic activities with mild side effects, for which they are considered new alternative antineoplastic drugs. However, the IC50 ranges of these complexes vary due to differences in their structure and solubility and their sensitivities for various cellular targets. Beta-cyclodextrin is an additive used to improve the solubility and stability of various drugs for therapeutic use, but the combination of beta-cyclodextrin with palladium (II) complexes and thiosemicarbazones has not been tested yet...
December 1, 2016: Biomédica: Revista del Instituto Nacional de Salud
https://www.readbyqxmd.com/read/27987496/-detection-of-peripheral-follicular-helper-t-cells-in-rheumatoid-arthritis
#16
L M An, J Li, L L Ji, G T Li, Z L Zhang
OBJECTIVE: To detect cell frequency and surface markers of peripheral CD4(+)CXCR5+ follicular helper T (Tfh) cells and analyze the correlation between CD4(+)CXCR5(+)Tfh cells and rheumatoid arthritis (RA) disease activity. METHODS: Forty RA patients meeting the American College of Rheumatology classification criteria for RA and twenty healthy controls (HC) were included. The peripheral blood mononuclear cells and sera were collected. The expressions of CD4+CXCR5(+)Tfh cells (CXCR5, C-X-C chemokine receptor type 5) and inducible T cell costimulator (ICOS), programmed death 1 positive (PD-1), interleukin-21 receptor (IL-21R) and CD40 ligand (CD40L) positive on CD4(+)CXCR5(+)Tfh cells were analyzed by flow cytometry...
December 18, 2016: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
https://www.readbyqxmd.com/read/27966604/endogenous-programmed-death-ligand-1-restrains-the-development-and-onset-of-sj%C3%B3-gren-s-syndrome-in-non-obese-diabetic-mice
#17
Jing Zhou, Jun-O Jin, Toshihisa Kawai, Qing Yu
Programmed death-ligand 1 (PD-L1) down-modulates various immune responses by engaging the co-inhibitory receptor programmed death-1. Expression of PD-L1 and programmed death-1 is elevated in the salivary glands of patients with Sjögren's syndrome (SS). The objective of this study is to define the role of endogenous PD-L1 in SS pathogenesis in non-obese diabetic (NOD) mouse model of this disease. We inhibited endogenous PD-L1 function by intraperitoneal administration of a blocking antibody to 6 week-old female NOD/ShiLtJ mice repeatedly during a 9-day period...
December 14, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27957685/trpm2-promotes-neurotoxin-mpp-mptp-induced-cell-death
#18
Yuyang Sun, Pramod Sukumaran, Senthil Selvaraj, Nicholas I Cilz, Anne Schaar, Saobo Lei, Brij B Singh
In neurons, Ca(2+) is essential for a variety of physiological processes that regulate gene transcription to neuronal growth and their survival. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridinium ions (MPP(+)) are potent neurotoxins that selectively destroys the dopaminergic (DA) neurons and mimics Parkinson's disease (PD) like symptoms, but the mechanism as how MPP(+)/MPTP effects DA neuron survival is not well-understood. In the present study, we found that MPP(+) treatment increased the level of reactive oxygen species (ROS) that activates and upregulates the expression and function of melastatin-like transient receptor potential (TRPM) subfamily member, melastatin-like transient receptor potential channel 2 (TRPM2)...
December 12, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27941289/immune-checkpoint-inhibitors-in-hematologic-malignancies
#19
Dai Maruyama
Immuno-checkpoint inhibitors are one of the most promising immunotherapies for various advanced cancers including hematologic malignancies. Recently, enhanced signaling of the PD-1/CTLA4 pathway has emerged as a critical mechanism by which tumors can escape the anti-tumor immune response. PD-1-blocking antibodies have been used to enhance immunity in several malignancies and obtain durable responses, especially in patients with heavily treated relapsed/refractory Hodgkin lymphoma. Currently, several clinical trials including single agent or combination therapies for hematologic malignancies, such as Hodgkin lymphoma, B-cell lymphomas and multiple myeloma, are ongoing...
2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/27933060/regulators-of-tfh-cell-differentiation
#20
REVIEW
Gajendra M Jogdand, Suchitra Mohanty, Satish Devadas
The follicular helper T (Tfh) cells help is critical for activation of B cells, antibody class switching, and germinal center (GC) formation. The Tfh cells are characterized by the expression of CXC chemokine receptor 5 (CXCR5), ICOS, programed death 1 (PD-1), B cell lymphoma 6 (BCL-6), and IL-21. They are involved in clearing infections and are adversely linked with autoimmune diseases and also have a role in viral replication as well as clearance. On the one hand, Tfh cells are generated from naive CD4(+) T cells with sequential steps involving cytokine signaling (IL-21, IL-6, IL-12, activin A), migration, and positioning in the GC by CXCR5, surface receptors (ICOS/ICOSL, signaling lymphocyte activation molecule-associated protein/signaling lymphocyte activation molecule) as well as transcription factor (BCL-6, c-Maf, and signal transducer and activator of transcription 3) signaling and repressor miR155...
2016: Frontiers in Immunology
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