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https://www.readbyqxmd.com/read/27925177/t-cell-diversification-reflects-antigen-selection-in-the-blood-of-patients-on-immune-checkpoint-inhibition-and-may-be-exploited-as-liquid-biopsy-biomarker
#1
Nuray Akyüz, Anna Brandt, Alexander Stein, Simon Schliffke, Thorben Mährle, Julia Quidde, Eray Goekkurt, Sonja Loges, Thomas Haalck, Christopher Ford, Anne Marie Asemissen, Benjamin Thiele, Janina Radloff, Toni Thenhausen, Artus Krohn-Grimberghe, Carsten Bokemeyer, Mascha Binder
Cancer immunotherapy with antibodies targeting immune checkpoints, such as programmed cell death protein 1 (PD-1), shows encouraging results, but reliable biomarkers predicting response to this costly and potentially toxic treatment approach are still lacking. To explore an immune signature predictive for response, we performed liquid biopsy immunoprofiling in 18 cancer patients undergoing PD-1 inhibition before and shortly after initiation of treatment by multicolor flow cytometry and next-generation T- and B-cell immunosequencing (TCRß/IGH)...
December 7, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27924752/predictive-biomarkers-for-checkpoint-inhibitor-based-immunotherapy
#2
REVIEW
Geoffrey T Gibney, Louis M Weiner, Michael B Atkins
The clinical development of checkpoint inhibitor-based immunotherapy has ushered in an exciting era of anticancer therapy. Durable responses can be seen in patients with melanoma and other malignancies. Although monotherapy with PD-1 or PD-L1 agents are typically well tolerated, the risk of immune-related adverse events increases with combination regimens. The development of predictive biomarkers is needed to optimise patient benefit, minimise risk of toxicities, and guide combination approaches. The greatest focus has been on tumour-cell PD-L1 expression...
December 2016: Lancet Oncology
https://www.readbyqxmd.com/read/27916626/impact-of-sequencing-targeted-therapies-with-high-dose-interleukin-2-immunotherapy-an-analysis-of-outcome-and-survival-of-patients-with-metastatic-renal-cell-carcinoma-from-an-on-going-observational-il-2-clinical-trial-proclaim-sm
#3
Joseph I Clark, Michael K K Wong, Howard L Kaufman, Gregory A Daniels, Michael A Morse, David F McDermott, Sanjiv S Agarwala, Lionel D Lewis, John H Stewart, Ulka Vaishampayan, Brendan Curti, René Gonzalez, Jose Lutzky, Venkatesh Rudraptna, Lee D Cranmer, Joanne M Jeter, Ralph J Hauke, Gerald Miletello, Mohammed M Milhem, Asim Amin, John M Richart, Mayer Fishman, Sigrun Hallmeyer, Sapna P Patel, Peter Van Veldhuizen, Neeraj Agarwal, Bret Taback, Jonathan S Treisman, Marc S Ernstoff, Jessica C Perritt, Hong Hua, Tharak B Rao, Janice P Dutcher, Sandra Aung
BACKGROUND: This analysis describes the outcome for patients who received targeted therapy (TT) prior to or following high-dose interleukin-2 (HD IL-2). PATIENTS AND METHODS: Patients with renal cell carcinoma (n = 352) receiving HD IL-2 were enrolled in Proleukin(R) Observational Study to Evaluate the Treatment Patterns and Clinical Response in Malignancy (PROCLAIM(SM)) beginning in 2011. Statistical analyses were performed using datasets as of September 24, 2015...
October 29, 2016: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/27895917/validation-of-biomarkers-to-predict-response-to-immunotherapy-in-cancer-volume-i-pre-analytical-and-analytical-validation
#4
REVIEW
Giuseppe V Masucci, Alessandra Cesano, Rachael Hawtin, Sylvia Janetzki, Jenny Zhang, Ilan Kirsch, Kevin K Dobbin, John Alvarez, Paul B Robbins, Senthamil R Selvan, Howard Z Streicher, Lisa H Butterfield, Magdalena Thurin
Immunotherapies have emerged as one of the most promising approaches to treat patients with cancer. Recently, there have been many clinical successes using checkpoint receptor blockade, including T cell inhibitory receptors such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death-1 (PD-1). Despite demonstrated successes in a variety of malignancies, responses only typically occur in a minority of patients in any given histology. Additionally, treatment is associated with inflammatory toxicity and high cost...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27892950/pd-1-checkpoint-blockade-in-patients-with-relapsed-aml-after-allogeneic-stem-cell-transplantation
#5
J C Albring, S Inselmann, T Sauer, C Schliemann, B Altvater, S Kailayangiri, C Rössig, W Hartmann, J R Knorrenschild, K Sohlbach, C Groth, M Lohoff, A Neubauer, W E Berdel, A Burchert, M Stelljes
No abstract text is available yet for this article.
November 28, 2016: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/27888360/identification-of-symplasmic-domains-in-the-embryo-and-seed-of-sedum-acre-l-crassulaceae
#6
Justyna Wróbel-Marek, Ewa Kurczyńska, Bartosz J Płachno, Małgorzata Kozieradzka-Kiszkurno
Our study demonstrated that symplasmic communication between Sedum acre seed compartments and the embryo proper is not uniform. The presence of plasmodesmata (PD) constitutes the structural basis for information exchange between cells, and symplasmic communication is involved in the regulation of cell differentiation and plant development. Most recent studies concerning an analysis of symplasmic communication between seed compartments and the embryo have been predominantly performed on Arabidopsis thaliana...
November 25, 2016: Planta
https://www.readbyqxmd.com/read/27887569/immune-modulation-of-cd4-cd25-regulatory-t-cells-by-zoledronic-acid
#7
Hsien Liu, Shih-Han Wang, Shin-Cheh Chen, Ching-Ying Chen, Jo-Lin Lo, Tsun-Mei Lin
BACKGROUND: CD4(+)CD25(+) regulatory T (Treg) cells suppress tumor immunity by inhibiting immune cells. Manipulation of Treg cells represents a new strategy for cancer treatment. Zoledronic acid (ZA), a nitrogen-containing bisphosphonate, inhibits the expression of receptor activator of nuclear factor kappa-B ligand (RANKL) on osteoblasts to inhibit osteoclastogenesis. In a mouse model of bisphosphonate-related osteonecrosis of the jaw, administration of ZA suppressed Treg-cell activity and activated inflammatory Th17 cells...
November 25, 2016: BMC Immunology
https://www.readbyqxmd.com/read/27882863/porphyromonas-gingivalis-suppresses-adaptive-immunity-in-periodontitis-atherosclerosis-and-alzheimer-s-disease
#8
REVIEW
Ingar Olsen, Martin A Taubman, Sim K Singhrao
Porphyromonas gingivalis, a keystone pathogen in chronic periodontitis, has been found to associate with remote body organ inflammatory pathologies, including atherosclerosis and Alzheimer's disease (AD). Although P. gingivalis has a plethora of virulence factors, much of its pathogenicity is surprisingly related to the overall immunosuppression of the host. This review focuses on P. gingivalis aiding suppression of the host's adaptive immune system involving manipulation of cellular immunological responses, specifically T cells and B cells in periodontitis and related conditions...
2016: Journal of Oral Microbiology
https://www.readbyqxmd.com/read/27882077/potential-protective-effects-of-autophagy-activated-in-mpp-treated-astrocytes
#9
Cunzhou Shen, Wenbiao Xian, Hongyan Zhou, Ling Chen, Zhong Pei
Astrocytes, which have various important functions, have previously been associated with Parkinsons disease (PD), particularly in 1-methyl-4-phenylpyridinium (MPP+) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) models of PD. MPP+ is the toxic metabolite of MPTP and is generated by the enzymatic activity of monoamine oxidase B, which is predominantly located in astrocytes. MPP+ acts as a mitochondrial complex I inhibitor. Autophagy is an evolutionarily conserved self-digestion pathway in eukaryotic cells, which occurs in response to various types of stress, including starvation and oxidative stress...
November 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27881328/immunostimulatory-capacity-of-dental-casting-alloys-on-endotoxin-responsiveness
#10
Dessy Rachmawati, B Mary E von Blomberg, Cornelis J Kleverlaan, Rik J Scheper, Ingrid M W van Hoogstraten
STATEMENT OF PROBLEM: Oral metal exposure has been associated with systemic and local adverse reactions, probably due to elemental release from the alloys. Although supraphysiological concentrations of salts from dentally applied metals can activate innate cells through TLR4 (Ni, Co, Pd) and TLR3 (Au), whether direct exposure to solid alloys can also trigger innate immune reactivity is still unknown. PURPOSE: The purpose of this in vitro study was to determine whether dental cast alloy specimens can activate innate cells and influence their responsiveness to bacterial endotoxin...
October 27, 2016: Journal of Prosthetic Dentistry
https://www.readbyqxmd.com/read/27880824/anti-invasive-and-anti-proliferative-synergism-between-docetaxel-and-a-polynuclear-pd-spermine-agent
#11
Ana L M Batista de Carvalho, Paula S C Medeiros, Francisco M Costa, Vanessa P Ribeiro, Joana B Sousa, Carmen Diniz, Maria P M Marques
The present work is aimed at evaluating the antitumour properties of a Pd(II) dinuclear complex with the biogenic polyamine spermine, by investigating: i) the anti-angiogenic and anti-migration properties of a Pd(II) dinuclear complex with spermine (Pd2Spm); ii) the anti-proliferative activity of Pd2Spm against a triple negative human breast carcinoma (MDA-MB-231); and finally iii) the putative interaction mediated by combination of Pd2Spm with Docetaxel. Anti-invasive (anti-angiogenic and anti-migratory) as well as anti-proliferative capacities were assessed, for different combination schemes and drug exposure times, using the CAM assay and VEGFR2 activity measurement, the MatrigelTM method and the SRB proliferation test...
2016: PloS One
https://www.readbyqxmd.com/read/27872741/novel-drugs-in-follicular-lymphoma
#12
REVIEW
Antonella Anastasia, Giuseppe Rossi
Follicular lymphoma(FL) is the most common indolent non-Hodgkin lymphoma and constitutes 15% to 30% of lymphoma diagnoses. The natural history of the disease is characterized by recurrent relapses and progressively shorter remissions with a median survival of 10yrs. The impossibility of achieving a definite cure, have prompted investigations into the possible role of more active and less toxic strategies with innovative therapeutic agents. Recently Casulo et al. demonstrated that approximately 20% of patients with FL relapse within two years after achieving remission with R-CHOP and have a poor prognosis...
2016: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/27865860/human-regulatory-b-cells-control-tfh-response
#13
Achouak Achour, Quentin Simon, Audrey Mohr, Jean-François Séité, Pierre Youinou, Boutahar Bendaoud, Ibtissem Ghedira, Jacques-Olivier Pers, Christophe Jamin
BACKGROUND: Follicular helper T (Tfh) cells support the terminal B-cell differentiation. Human regulatory B (Breg) cells modulate cellular responses but their control of Tfh-dependent humoral immune responses is unknown. OBJECTIVE: To assess the role of Breg cells on Tfh development and function. METHODS: Human T cells were polyclonally stimulated in the presence of IL-12 and IL-21 to generate Tfh cells. They were co-cultured with B cells to induce their terminal differentiation...
November 16, 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27865385/the-characteristic-profiles-of-pd-1-and-pd-l1-expressions-and-dynamic-changes-during-treatment-in-active-tuberculosis
#14
Lei Shen, Hong Shi, Yan Gao, Qinfang Ou, Qianqian Liu, Yuanyuan Liu, Jing Wu, Wenhong Zhang, Lin Fan, Lingyun Shao
PD-1 is a cell surface receptor of activated T and B lymphocytes and it's role in tuberculosis is controversial because of lack of congruence between clinical study and animal model. To investigate the immunological pathogenesis mechanisms of tuberculosis and to develop the immune therapy target essential for controlling tuberculosis, here we explored the expression characteristics and dynamic changes of PD-1/PD-L1 pathway in different CD4+T cell subsets. We enrolled 24 human subjects including 15 active tuberculosis (ATB) patients and 9 healthy donors (HD)...
December 2016: Tuberculosis
https://www.readbyqxmd.com/read/27864219/neoadjuvant-chemotherapy-nact-increases-immune-infiltration-and-programmed-death-ligand-1-pd-l1-expression-in-epithelial-ovarian-cancer-eoc
#15
S J L Mesnage, A Auguste, C Genestie, A Dunant, E Pain, F Drusch, S Gouy, P Morice, E Bentivegna, C Lhomme, P Pautier, J Michels, A Le Formal, B Cheaib, J Adam, A F Leary
BACKGROUND: Lymphocytic infiltration at diagnosis is prognostic in EOC, however the impact of NACT on tumour infiltrating lymphocytes (TILs) or PD-L1 expression remains poorly described. PATIENTS AND METHODS: Patients with EOC and sequential samples (pre-NACT, post-NACT or relapse) were retrospectively identified. TILs were evaluated on whole sections; stromal TILs (sTILs) scored as percentage of stromal area with high sTILs defined as ≥50%; intra-epithelial TILs (ieTILs) scored semi-quantitatively (0-3) with high ieTILs ≥2...
November 17, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/27863842/development-of-t-follicular-helper-cells-and-their-role-in-disease-and-immune-system
#16
REVIEW
Sadegh Eivazi, Salman Bagheri, Mohammad Sadegh Hashemzadeh, Majdedin Ghalavand, Elmira Safaie Qamsari, Ruhollah Dorostkar, Maryam Yasemi
The T follicular helper cells (TFH) are a subset of CD4+ T cells specialized to regulate antibody responses. The production of these cells is associated with the dendritic cells (DCs) and B cells. TFH cells help B cells form germinal centers (GC) differentiate into memory and plasma cells (antibody-secreting cells) as humoral responses. In addition, there is strong evidence that TFH cells play a pivotal role in the development of long-lived humoral immunity. Molecular factors such as transcription factors, surface receptors, cytokine and micro RNAs are involved in the formation of TFH cells...
November 15, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27861596/pd-l1-status-in-refractory-lymphomas
#17
Semir Vranic, Nilanjan Ghosh, Jeffery Kimbrough, Nurija Bilalovic, Ryan Bender, David Arguello, Yvonne Veloso, Aida Dizdarevic, Zoran Gatalica
Targeted immunotherapy based on PD-1/PD-L1 suppression has revolutionized the treatment of various solid tumors. A remarkable improvement has also been observed in the treatment of patients with refractory/relapsing classical Hodgkin lymphoma (cHL). We investigated PD-L1 status in a variety of treatment resistant lymphomas. Tumor samples from 78 patients with therapy resistant lymphomas were immunohistochemically (IHC) investigated for the expression of PD-L1 using two antibody clones (SP142 and SP263, Ventana)...
2016: PloS One
https://www.readbyqxmd.com/read/27856425/pd-1-suppresses-development-of-humoral-responses-that-protect-against-tn-bearing-tumors
#18
Marcela A Haro, Chad A Littrell, Zhaojun Yin, Xuefei Huang, Karen M Haas
Tn is a carbohydrate antigen uniquely exposed on tumor mucins and, thus, an ideal target for immunotherapy. However, it has been difficult to elicit protective antibody responses against Tn antigen and other tumor-associated carbohydrate antigens. Our study demonstrates this can be attributed to PD-1 immuno-inhibition. Our data show a major role for PD-1 in suppressing mucin- and Tn-specific B-cell activation, expansion, and antibody production important for protection against Tn-bearing tumor cells. These Tn/mucin-specific B cells belong to the innate-like B-1b cell subset typically responsible for T cell-independent antibody responses...
December 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27846724/-the-role-of-pd-1-pd-l1-signaling-pathway-in-antitumor-immune-response
#19
P Zatloukalová, M Pjechová, S Babčanová, T R Hupp, B Vojtěšek
BACKGROUND: Correct function of the immune system depends on close cooperation between stimulation and inhibition signals, which protect an organism from outside microorganisms and other agents, but also protects healthy tissues against possible self-destructing attacks of the immune system. However, the inhibitory mechanisms can be abused by cancer cells that evade immune responses and, in fact, they help develop cancer. Therefore, one of the characteristics of cancer cells is the ability to evade immune recognition...
2016: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/27846054/sequencing-treatment-in-brafv600-mutant-melanoma-anti-pd-1-before-and-after-braf-inhibition
#20
Douglas B Johnson, Eirini Pectasides, Emily Feld, Fei Ye, Shilin Zhao, Romany Johnpulle, Ryan Merritt, David F McDermott, Igor Puzanov, Donald Lawrence, Jeffrey A Sosman, Elizabeth Buchbinder, Ryan J Sullivan
Novel agents targeting immune checkpoint molecules or mutated BRAF are active therapeutic options for patients with BRAF-mutant melanoma. However, the most effective first-line treatment and the optimal sequencing of these agents have not been well characterized. To explore this, we retrospectively assessed 114 patients from 4 centers with advanced, BRAF-mutant melanoma who received anti-programmed cell death-1 (PD-1)/PD-L1 antibodies. We evaluated clinical outcomes, including objective response rate (ORR), overall survival (OS), and progression-free survival (PFS) to initial and subsequent therapies in patients that received anti-PD-1 first (n=56) versus those that received BRAF±MEK inhibitors (BRAFi) first (n=58)...
January 2017: Journal of Immunotherapy
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