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https://www.readbyqxmd.com/read/28750133/role-of-cytotoxic-tumor-infiltrating-lymphocytes-in-predicting-outcomes-in-metastatic-her2-positive-breast-cancer-a-secondary-analysis-of-a-randomized-clinical-trial
#1
Shuzhen Liu, Bingshu Chen, Samantha Burugu, Samuel Leung, Dongxia Gao, Shakeel Virk, Zuzana Kos, Wendy R Parulekar, Lois Shepherd, Karen A Gelmon, Torsten O Nielsen
Importance: Accumulating evidence indicates that tumor-infiltrating lymphocytes (TILs) are associated with clinical outcomes and may predict the efficacy of chemotherapy and human epidermal growth factor receptor 2 (HER2, encoded by the gene ERBB2)-targeted therapy in patients with HER2-positive breast cancer. Objective: To investigate the role of TILs, particularly cytotoxic CD8+ T cells, in the prediction of outcomes in patients with HER2-positive metastatic breast cancer randomized to an antibody-based (trastuzumab) vs a small molecule-based (lapatinib) anti-HER2 therapy...
July 27, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28750018/pancreatic-cancer-cell-fibroblast-co-culture-induces-m2-like-macrophages-that-influence-therapeutic-response-in-a-3d-model
#2
Janina Kuen, Diana Darowski, Tobias Kluge, Meher Majety
Pancreatic cancer (PC) remains one of the most challenging solid tumors to treat with a high unmet medical need as patients poorly respond to standard-of-care-therapies. Prominent desmoplastic reaction involving cancer-associated fibroblasts (CAFs) and the immune cells in the tumor microenvironment (TME) and their cross-talk play a significant role in tumor immune escape and progression. To identify the key cellular mechanisms induce an immunosuppressive tumor microenvironment, we established 3D co-culture model with pancreatic cancer cells, CAFs and monocytes...
2017: PloS One
https://www.readbyqxmd.com/read/28749465/acid-sphingomyelinase-mediates-human-cd4-t-cell-signaling-potential-roles-in-t-cell-responses-and-diseases
#3
REVIEW
Aiping Bai, Yuan Guo
Acid sphingomyelinase (ASM) is a lipid hydrolase. By generating ceramide, ASM had been reported to have an important role in regulating immune cell functions inclusive of macrophages, NK cells, and CD8(+) T cells, whereas the role of ASM bioactivity in regulation of human CD4(+) T-cell functions remained uncertain. Recent studies have provided novel findings in this field. Upon stimulation of CD3 and/or CD28, ASM-dependent ceramide signaling mediates intracellular downstream signal cascades of CD3 and CD28, and regulates CD4(+) T-cell activation and proliferation...
July 27, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28749311/reconstitution-of-the-peripheral-immune-repertoire-following-withdrawal-of-fingolimod
#4
Mahtab Ghadiri, Leslie Fitz-Gerald, Ayman Rezk, Rui Li, Mukanthu Nyirenda, David Haegert, Paul Steven Giacomini, Amit Bar-Or, Jack Antel
BACKGROUND: Following fingolimod cessation, immune reconstitution or lack thereof may have consequences for disease rebound or safety of commencing alternative therapies. OBJECTIVE: To examine the degree and profile of peripheral blood lymphocyte reconstitution following fingolimod withdrawal. METHODS: Total lymphocyte counts (TLC) and CD4+/CD8+ T-cell counts were measured in 18 multiple sclerosis (MS) patients pre-treatment, on fingolimod, and up to 8-9 months post-cessation...
August 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28749113/increased-tumour-infiltration-of-cd4-and-cd8-t-lymphocytes-in-patients-with-triple-negative-breast-cancer-suggests-susceptibility-to-immune-therapy
#5
Bushra Sikandar, Muhammad Asif Qureshi, Saima Naseem, Saeed Khan, Talat Mirza
Background: Patients with triple negative breast cancer (TNBC) have limited therapeutic options, largely because the complex tumour environment is not well-characterized. These patients are potential, but largely un-fathomed, candidates for immunotherapy. It is therefore highly relevant to characterize leukocyte complexity in TNBCs. Objective: To investigate leukocyte complexity in tumour environment of patients with TNBCs. Materials and methods: A total of 104 consecutive breast cancer patients undergoing mastectomy were recruited in the study after ethical approval...
July 27, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28747914/extrinsic-protein-tyrosine-phosphatase-non-receptor-22-signals-contribute-to-cd8-t-cell-exhaustion-and-promote-persistence-of-chronic-lymphocytic-choriomeningitis-virus-infection
#6
Tatiana Jofra, Giuseppe Galvani, Mirela Kuka, Roberta Di Fonte, Bechara G Mfarrej, Matteo Iannacone, Shahram Salek-Ardakani, Manuela Battaglia, Georgia Fousteri
A genetic variant of the protein tyrosine phosphatase non-receptor 22 (PTPN22) is associated with a wide range of autoimmune diseases; however, the reasons behind its prevalence in the general population remain not completely understood. Recent evidence highlights an important role of autoimmune susceptibility genetic variants in conferring resistance against certain pathogens. In this study, we examined the role of PTPN22 in persistent infection in mice lacking PTPN22 infected with lymphocytic choriomeningitis virus clone 13...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28747613/increased-carotid-artery-lesion-inflammation-upon-treatment-with-the-cd137-agonistic-antibody-2a
#7
Leif Å Söderström, Hong Jin, April S Caravaca, Maria L Klement, Yuhuang Li, Anton Gisterå, Ulf Hedin, Lars Maegdefessel, Göran K Hansson, Peder S Olofsson
BACKGROUND: Increased inflammatory activity destabilizes the atherosclerotic lesion and may lead to atherothrombosis and symptomatic cardiovascular disease. Co-stimulatory molecules, such as CD137, are key regulators of inflammation, and CD137 activity regulates inflammation in experimental atherosclerosis. Here, we hypothesized that CD137 activation promotes carotid artery inflammation and atherothrombosis.Methods and Results:In a model of inducible atherothrombosis with surgical ligation of the right carotid artery and a subsequent placement of a polyethene cuff, elevated levels of CD137 and CD137 ligand mRNA in atherothrombotic vs...
July 26, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/28747505/insufficient-innate-immunity-contributes-to-the-susceptibility-of-the-castaneous-mouse-to-orthopoxvirus-infection
#8
Patricia L Earl, Jeffrey L Americo, Bernard Moss
The castaneous (CAST) mouse, a wild-derived inbred strain, is highly susceptible to orthopoxvirus infection by intranasal and systemic routes. The 50% lethal intraperitoneal dose of vaccinia virus (VACV) was 3 PFU for CAST mice, whereas BALB/c mice survived 10(6) PFU. At all times and in all organs analyzed, virus titers were higher in CAST than in BALB/c mice. In individual CAST mice, luciferase-expressing VACV was seen to replicate rapidly leading to death, whereas virus levels increased for a few days and then declined in BALB/c mice...
July 26, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28746871/the-histone-methyltransferase-ezh2-controls-mechanisms-of-adaptive-resistance-to-tumor-immunotherapy
#9
Daniel Zingg, Natalia Arenas-Ramirez, Dilara Sahin, Rodney A Rosalia, Ana T Antunes, Jessica Haeusel, Lukas Sommer, Onur Boyman
Immunotherapy and particularly immune checkpoint inhibitors have resulted in remarkable clinical responses in patients with immunogenic tumors, although most cancers develop resistance to immunotherapy. The molecular mechanisms of tumor resistance to immunotherapy remain poorly understood. We now show that induction of the histone methyltransferase Ezh2 controls several tumor cell-intrinsic and extrinsic resistance mechanisms. Notably, T cell infiltration selectively correlated with high EZH2-PRC2 complex activity in human skin cutaneous melanoma...
July 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28746799/lack-of-il-6-in-the-tumor-microenvironment-augments-type-1-immunity-and-increases-the-efficacy-of-cancer-immunotherapy
#10
Yosuke Ohno, Yujiro Toyoshima, Hideaki Yurino, Norikazu Monma, Huihui Xiang, Kentaro Sumida, Shun Kaneumi, Satoshi Terada, Shinichi Hashimoto, Kazuho Ikeo, Shigenori Homma, Hideki Kawamura, Norihiko Takahashi, Akinobu Taketomi, Hidemitsu Kitamura
Conquering immunosuppression in tumor microenvironments is crucial for effective cancer immunotherapy. It is well known that interleukin (IL)-6, a pleiotropic cytokine, is produced in the tumor-bearing state. In this study, we investigated the precise effects of IL-6 on antitumor immunity and the subsequent tumorigenesis in tumor-bearing hosts. CT26 cells, a murine colon cancer cell line, were intradermally injected into wild-type and IL-6-deficient mice. As a result, we found that tumor growth was decreased significantly in IL-6-deficient mice compared with wild-type mice and the reduction was abrogated by depletion of CD8(+) T cells...
July 26, 2017: Cancer Science
https://www.readbyqxmd.com/read/28746446/t-lymphocytes-and-macrophages-in-the-intestinal-tissues-of-dogs-infected-with-leishmania-infantum
#11
Diogo Tiago da Silva, Maria Luana Alves, Júlio Cesar Pereira Spada, Aline Cristine da Silva, Rita de Cássia Viveiros da Silveira, Trícia Maria Ferreira de Sousa Oliveira, Wilma Aparecida Starke-Buzetti
This study was about a semi-quantitative analysis of T lymphocytes (CD4+ and CD8+, FoxP3+ regulatory T cells), and macrophages in the gut wall of dogs naturally infected with Leishmania infantum. Thirteen dogs were divided into three groups: group 1 (G1, n=5), dogs with canine visceral leishmaniasis (CVL) and infected with L. infantum amastigotes in the intestine; group 2 (G2, n=5), dogs with CVL but without intestinal amastigotes; and group 3 (G3, n=3), uninfected dogs (control group). There was no significant difference (p ≥ 0...
April 2017: Revista Brasileira de Parasitologia Veterinária, Brazilian Journal of Veterinary Parasitology
https://www.readbyqxmd.com/read/28745327/seminal-vesicle-fluid-increases-the-efficacy-of-intravaginal-hsv-2-vaccination
#12
A Varese, F Remes Lenicov, M Gonzalez Prinz, A Paletta, G Ernst, C Maeto, A Merlotti, J Sabatte, S Símula, M P Holgado, E Dantas, J Geffner, A Ceballos
Once considered merely as a vehicle for spermatozoa, it is now clear that seminal plasma (SP) induces a variety of biological actions on the female reproductive tissues able to modulate the immune response against paternal antigens. To our knowledge, the influence of SP on the immune response against sexually transmitted pathogens has not been yet evaluated. We here analyzed whether the seminal vesicle fluid (SVF), which contributes almost 60% of the SP volume in mice, could modulate the immune response against herpes simplex virus type 2 (HSV-2)...
July 26, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28744286/a-b-cell-driven-autoimmune-pathway-leading-to-pathological-hallmarks-of-progressive-multiple-sclerosis-in-the-marmoset-experimental-autoimmune-encephalomyelitis-model
#13
REVIEW
Bert A 't Hart, Jordon Dunham, Bart W Faber, Jon D Laman, Jack van Horssen, Jan Bauer, Yolanda S Kap
The absence of pathological hallmarks of progressive multiple sclerosis (MS) in commonly used rodent models of experimental autoimmune encephalomyelitis (EAE) hinders the development of adequate treatments for progressive disease. Work reviewed here shows that such hallmarks are present in the EAE model in marmoset monkeys (Callithrix jacchus). The minimal requirement for induction of progressive MS pathology is immunization with a synthetic peptide representing residues 34-56 from human myelin oligodendrocyte glycoprotein (MOG) formulated with a mineral oil [incomplete Freund's adjuvant (IFA)]...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28743486/targeting-interferon-alpha-to-dendritic-cells-enhances-a-cd8-t-cell-response-to-a-human-cd40-targeted-cancer-vaccine
#14
John P Graham, Pierre Authie, A Karolina Palucka, Gerard Zurawski
Targeting antigens to antigen presenting cells (APC) enhances the potency of recombinant protein CD8(+) T cell vaccines. Recent comparisons of recombinant protein-based dendritic cell (DC) targeting vaccines revealed differences in cross-presentation and identified CD40 as a potent human DC receptor target for antigen cross-presentation. Contrary to in vitro-derived monocyte (mo)DC, we found that interferon-alpha (IFNα) stimulation of human blood-derived DC was necessary for an antigen-specific IFNγ CD8(+) T cell response to a CD40 targeted cancer vaccine...
July 22, 2017: Vaccine
https://www.readbyqxmd.com/read/28743332/-clinical-significance-of-early-immunological-paralysis-in-patients-with-severe-h1n1-influenza-a
#15
Yongbing Qian, Hui Xie, Rui Tian, Jian Lu, Wei Jin, Ruilan Wang
OBJECTIVE: To analysis the immunological characteristics of patients with severe H1N1 influenza A, and to provide theoretical basis for predicting the prognosis of the disease. METHODS: A retrospective analysis was conducted. The clinical data of 15 patients diagnosed with severe H1N1 influenza A and admitted to Shanghai General Hospital of Nanjing Medical University from October 2015 to December 2016 were collected. All the patients were divided into survival and death groups according to 28-day survival...
July 2017: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/28743289/inhibition-of-t-cell-mediated-inflammation-in-uveitis-by-a-novel-anti-cd3-antibody
#16
Sunao Sugita, Jun Shimizu, Kenichi Makabe, Hiroshi Keino, Takeshi Watanabe, Masayo Takahashi
BACKGROUND: A novel anti-mouse CD3ε antibody, Dow2, recognizes mouse CD3ε without activating T cells and suppresses T-cell activation. The purpose of this study was to determine whether Dow2 can inhibit T cells in uveitis. METHODS: Experimental autoimmune uveitis (EAU) was induced in mice by immunization with retinal peptides, followed by administration of Dow2. Inflammation was evaluated by color fundus photography, optical coherence tomography, fluorescein angiography, and histology...
July 25, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28742212/relevant-researches-on-chronic-viral-myocarditis-cvmc-in-children-complicated-with-arrhythmia-and-thyroid-hormone-level
#17
M-Y Fu, Q-W Wang, Y Xue, F Xu, C-L Li, X-J An
OBJECTIVE: To analyze the correlation between chronic viral myocarditis (CVMC) in children, complicated with arrhythmia and thyroid hormone level. PATIENTS AND METHODS: 60 patients with CVMC complicated with arrhythmia were continuously selected (course of disease > 3 months) and they are were diagnosed with arrhythmia by the routine 18-lead electrocardiogram and 24-hour Holter; the average follow-up time is about 2 years, during which the left ventricular end-diastolic diameter (LVEDd), left ventricular ejection fraction (LVEF), the occurrence rate of malignant arrhythmia events, immune state of T cell and thyroid hormone level (FT3, FT4, TSH, TGAb and TPOAb) were compared...
July 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28742190/the-research-on-the-influences-of-hyperthermal-perfusion-chemotherapy-combined-with-immunologic-therapy-on-the-immunologic-function-and-levels-of-circulating-tumor-cells-of-the-advanced-colorectal-cancer-patients-with-liver-metastasis
#18
J-J Sun, G-L Fan, X-G Wang, K Xu
OBJECTIVE: To investigated the influence of hyperthermal perfusion chemotherapy combined with immunologic therapy on the immunologic function and levels of circulating tumor cells of the advanced colorectal cancer patients with liver metastasis. PATIENTS AND METHODS: We enrolled 98 advanced colorectal cancer patients with liver metastasis that were admitted to this hospital for treatment and were randomly divided into two groups, the observation group (n = 49) and the control group (n = 49)...
July 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28741316/role-of-cd4-t-cell-helper-subsets-in-immune-response-and-deviation-of-cd8-t-cells-in-mice
#19
Alison Hogg, Yongjun Sui, Shlomo Z Ben-Sasson, William E Paul, Jay A Berzofsky
The ability of different CD4(+) T cell subsets to help CD8(+) T-cell response is not fully understood. Here, we found using the murine system that Th17 cells induced by IL-1β, unlike Th1, were not effective helpers for antiviral CD8 responses as measured by IFNγ-producing cells or protection against virus infection. However, they skewed CD8 responses to a Tc17 phenotype. Thus, the apparent lack of help was actually immune deviation. This skewing depended on both IL-21 and IL-23. To overcome this effect, we inhibited Th17 induction by blocking TGF-β...
July 24, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28740491/nod-like-receptor-p3-inflammasome-controls-protective-th1-th17-immunity-against-pulmonary-paracoccidioidomycosis
#20
Claudia Feriotti, Eliseu Frank de Araújo, Flavio Vieira Loures, Tania Alves da Costa, Nayane Alves de Lima Galdino, Dario Simões Zamboni, Vera Lucia Garcia Calich
The NOD-like receptor P3 (NLRP3) inflammasome is an intracellular multimeric complex that triggers the activation of inflammatory caspases and the maturation of IL-1β and IL-18, important cytokines for the innate immune response against pathogens. The functional NLRP3 inflammasome complex consists of NLRP3, the adaptor protein apoptosis-associated speck-like protein, and caspase-1. Various molecular mechanisms were associated with NLRP3 activation including the presence of extracellular ATP, recognized by the cell surface P2X7 receptor (P2X7R)...
2017: Frontiers in Immunology
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