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https://www.readbyqxmd.com/read/27912781/an-immune-stratification-reveals-a-subset-of-pd-1-lag-3-double-positive-triple-negative-breast-cancers
#1
Giulia Bottai, Carlotta Raschioni, Agnese Losurdo, Luca Di Tommaso, Corrado Tinterri, Rosalba Torrisi, Jorge S Reis-Filho, Massimo Roncalli, Christos Sotiriou, Armando Santoro, Alberto Mantovani, Sherene Loi, Libero Santarpia
BACKGROUND: Stromal tumor-infiltrating lymphocytes (TILs) are a robust prognostic factor in triple-negative breast cancer (TNBC). However, the clinical significance of TILs may be influenced by the complex landscape of the tumor immune microenvironment. In this study, we aimed to evaluate the composition and the functionality of lymphocytic infiltration and checkpoint receptors in TNBC. METHODS: Formalin-fixed, paraffin-embedded tissues were retrospectively collected from a cohort of patients with early-stage TNBC treated with adjuvant anthracycline-based chemotherapy (n = 259)...
December 3, 2016: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/27903721/cross-talk-between-brain-innate-immunity-and-serotonin-signaling-underlies-depressive-like-behavior-induced-by-alzheimer-s-amyloid-%C3%AE-oligomers-in-mice
#2
Jose Henrique Ledo, Estefania P Azevedo, Danielle Beckman, Felipe C Ribeiro, Luis E Santos, Daniela S Razolli, Grasielle C Kincheski, Helen M Melo, Maria Bellio, Antonio L Teixeira, Licio A Velloso, Debora Foguel, Fernanda G De Felice, Sergio T Ferreira
: Considerable clinical and epidemiological evidence links Alzheimer's disease (AD) and depression. However, the molecular mechanisms underlying this connection are largely unknown. We reported recently that soluble Aβ oligomers (AβOs), toxins that accumulate in AD brains and are thought to instigate synapse damage and memory loss, induce depressive-like behavior in mice. Here, we report that the mechanism underlying this action involves AβO-induced microglial activation, aberrant TNF-α signaling, and decreased brain serotonin levels...
November 30, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27890077/t-lymphocyte-immunophenotypes-in-the-cerebrospinal-fluid-of-dogs-with-visceral-leishmaniasis
#3
Fernanda G Grano, José Eduardo Dos S Silva, Guilherme D Melo, Juliana Perosso, Valéria M F Lima, Gisele F Machado
Visceral leishmaniasis (VL) is a disease causing several clinical manifestations in dogs, including neurological disorders. Nevertheless, there are few studies related to the evaluation of the brain alterations during VL. Evidences of the involvement of cerebral barriers in infected dogs was reported, including the presence of brain inflammatory infiltrate, with a predominance of CD3+ T cells. Therefore, the aim of this study was to determine the immunophenotypes of T lymphocytes in the cerebrospinal fluid (CSF), as well as in peripheral blood, and to correlate with brain alterations in dogs with VL...
December 15, 2016: Veterinary Parasitology
https://www.readbyqxmd.com/read/27873237/estimating-long-term-survival-of-adults-with-philadelphia-chromosome-negative-relapsed-refractory-b-precursor-acute-lymphoblastic-leukemia-treated-with-blinatumomab-using-historical-data
#4
Arie Barlev, Vincent W Lin, Aaron Katz, Kuolung Hu, Ze Cong, Beth Barber
INTRODUCTION: Blinatumomab is a bispecific T cell-engaging antibody construct indicated for adult patients with relapsed/refractory (R/R) Ph(-) B-precursor acute lymphoblastic leukemia (ALL), an aggressive disease with poor prognosis. A phase 2 single-arm clinical study showed that 43% of patients achieved CR/CRh within two cycles and approximately 20% of patients receiving blinatumomab were still alive after 2 years. METHODS: The objective of the current analysis was to estimate long-term survival of patients receiving blinatumomab beyond the observed time period in the clinical study using a large historical observational dataset...
November 21, 2016: Advances in Therapy
https://www.readbyqxmd.com/read/27872100/regeneration-of-cd8%C3%AE-%C3%AE-t-cells-from-t-cell-derived-ipsc-imparts-potent-tumor-antigen-specific-cytotoxicity
#5
Takuya Maeda, Seiji Nagano, Hiroshi Ichise, Keisuke Kataoka, Daisuke Yamada, Seishi Ogawa, Haruhiko Koseki, Toshio Kitawaki, Norimitsu Kadowaki, Akifumi Takaori-Kondo, Kyoko Masuda, Hiroshi Kawamoto
Although adoptive transfer of cytotoxic T lymphocytes (CTL) offer a promising cancer therapeutic direction, the generation of antigen-specific CTL from patients has faced difficulty in efficient expansion in ex vivo culture. To resolve this issue, several groups have proposed that induced pluripotent stem cell technology be applied for the expansion of antigen-specific CTL, which retain expression of the same T-cell receptor as original CTL. However, in these previous studies, the regenerated CTL are mostly of the CD8αα(+) innate type and have less antigen-specific cytotoxic activity than primary CTL...
December 1, 2016: Cancer Research
https://www.readbyqxmd.com/read/27870882/immune-activation-at-sites-of-hiv-tb-co-infection-contributes-to-the-pathogenesis-of-hiv-1-disease
#6
Qinglai Meng, Ismail Sayin, David H Canaday, Harriet Mayanja-Kizza, Joy Baseke, Zahra Toossi
Systemic immune activation is critical to the pathogenesis of HIV-1 disease, and is accentuated in HIV/TB co-infected patients. The contribution of immune activation at sites of HIV/TB co-infection to viral activity, CD4 T cell count, and productive HIV-1 infection remain unclear. In this study, we measured markers of immune activation both in pleural fluid and plasma, and in T cells in pleural fluid mononuclear cell (PFMC) and peripheral blood mononuclear cell (PBMC) in HIV/TB co-infected subjects. The relationship between soluble and T cell activation markers with viral load in pleural fluid and blood CD4 T cell count were assessed...
2016: PloS One
https://www.readbyqxmd.com/read/27856426/cytotoxic-t-cells-in-pd-l1-positive-malignant-pleural-mesotheliomas-are-counterbalanced-by-distinct-immunosuppressive-factors
#7
Mark M Awad, Robert E Jones, Hongye Liu, Patrick H Lizotte, Elena V Ivanova, Meghana Kulkarni, Grit S Herter-Sprie, Xiaoyun Liao, Abigail A Santos, Mark A Bittinger, Lauren Keogh, Shohei Koyama, Christina Almonte, Jessie M English, Julianne Barlow, William G Richards, David A Barbie, Adam J Bass, Scott J Rodig, F Stephen Hodi, Kai W Wucherpfennig, Pasi A Jänne, Lynette M Sholl, Peter S Hammerman, Kwok-Kin Wong, Raphael Bueno
PD-L1 immunohistochemical staining does not always predict whether a cancer will respond to treatment with PD-1 inhibitors. We sought to characterize immune cell infiltrates and the expression of T-cell inhibitor markers in PD-L1-positive and PD-L1-negative malignant pleural mesothelioma samples. We developed a method for immune cell phenotyping using flow cytometry on solid tumors that have been dissociated into single-cell suspensions and applied this technique to analyze 43 resected malignant pleural mesothelioma specimens...
December 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27852740/temporal-expression-of-bim-limits-the-development-of-agonist-selected-thymocytes-and-skews-their-tcr%C3%AE-repertoire
#8
Kun-Po Li, Anke Fähnrich, Eron Roy, Carla M Cuda, H Leighton Grimes, Harris R Perlman, Kathrin Kalies, David A Hildeman
CD8αα TCRαβ(+) intestinal intraepithelial lymphocytes play a critical role in promoting intestinal homeostasis, although mechanisms controlling their development and peripheral homeostasis remain unclear. In this study, we examined the spatiotemporal role of Bim in the thymic selection of CD8αα precursors and the fate of these cells in the periphery. We found that T cell-specific expression of Bim during early/cortical, but not late/medullary, thymic development controls the agonist selection of CD8αα precursors and limits their private TCRβ repertoire...
November 16, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27852267/culture-expansion-of-adipose-derived-stromal-cells-a-closed-automated-quantum-cell-expansion-system-compared-with-manual-flask-based-culture
#9
Mandana Haack-Sørensen, Bjarke Follin, Morten Juhl, Sonja K Brorsen, Rebekka H Søndergaard, Jens Kastrup, Annette Ekblond
BACKGROUND: Adipose derived stromal cells (ASCs) are a rich and convenient source of cells for clinical regenerative therapeutic approaches. However, applications of ASCs often require cell expansion to reach the needed dose. In this study, cultivation of ASCs from stromal vascular fraction (SVF) over two passages in the automated and functionally closed Quantum Cell Expansion System (Quantum system) is compared with traditional manual cultivation. METHODS: Stromal vascular fraction was isolated from abdominal fat, suspended in α-MEM supplemented with 10% Fetal Bovine Serum and seeded into either T75 flasks or a Quantum system that had been coated with cryoprecipitate...
November 16, 2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27848183/an-atypical-case-of-late-onset-systemic-lupus-erythematosus-with-systemic-lymphadenopathy-and-severe-autoimmune-thrombocytopenia-neutropenia-mimicking-malignant-lymphoma
#10
Keita Tamaki, Satoko Morishima, Sawako Nakachi, Sakiko Kitamura, Sachie Uchibori, Shouhei Tomori, Taeko Hanashiro, Natsuki Shimabukuro, Iori Tedokon, Kazuho Morichika, Yukiko Nishi, Takeaki Tomoyose, Kennosuke Karube, Takuya Fukushima, Hiroaki Masuzaki
Here, we report a rare case of systemic lupus erythematosus (SLE) with conspicuous manifestation of hematological abnormalities. At onset, the 52-year-old male patient showed systemic lymphadenopathy and splenomegaly, severe autoimmune thrombocytopenia, and autoimmune neutropenia. Bone marrow examination and lymph node biopsy excluded the possibility of malignant lymphoma. Based on laboratory findings, he was finally diagnosed with combined autoimmune cytopenia coupled with SLE. Atypical clinical manifestations of SLE prompted us to explore the possibility of autoimmune lymphoproliferative syndrome (ALPS)...
November 15, 2016: International Journal of Hematology
https://www.readbyqxmd.com/read/27848181/characterization-of-circulating-cd4-cd8-double-positive-and-cd4-cd8-double-negative-t-lymphocyte-in-children-with-%C3%AE-thalassemia-major
#11
Asmaa M Zahran, Khaled Saad, Khalid I Elsayh, Mohamd A Alblihed
: Infectious complications represent the second most common cause of mortality and a major cause of morbidity in β-thalassemia major (BTM), with a prevalence of 12-13%. The data on unconventional T-lymphocyte subsets in BTM children are limited. The aim of the present study was to investigate and evaluate phenotypic alterations in CD4(+)CD8(+) double positive (DP), CD4(-) CD8(-) double negative (DN), and natural killer T-lymphocytes (NKT) in BTM children in comparison to healthy controls...
November 15, 2016: International Journal of Hematology
https://www.readbyqxmd.com/read/27846610/bone-marrow-findings-in-autoimmune-lymphoproliferative-syndrome-with-germline-fas-mutation
#12
Yi Xie, Stefania Pittaluga, Susan Price, Mark Raffeld, Jamie Hahn, Elaine S Jaffe, V Koneti Rao, Irina Maric
Autoimmune lymphoproliferative syndrome is rare genetic disorder characterized by defective FAS-mediated apoptosis, autoimmune disease, accumulation of mature T-cell receptor alpha/beta positive, CD4 and CD8 double-negative T cells and increased risk for lymphoma. Despite frequent hematological abnormalities, literature is scarce regarding the bone marrow pathology in autoimmune lymphoproliferative syndrome. We retrospectively reviewed 3l bone marrow biopsies from a cohort of 240 patients with germline FAS mutation...
October 20, 2016: Haematologica
https://www.readbyqxmd.com/read/27837111/age-associated-b-cells-with-proinflammatory-characteristics-are-expanded-in-a-proportion-of-multiple-sclerosis-patients
#13
Nele Claes, Judith Fraussen, Marjan Vanheusden, Niels Hellings, Piet Stinissen, Bart Van Wijmeersch, Raymond Hupperts, Veerle Somers
Immune aging occurs in the elderly and in autoimmune diseases. Recently, IgD(-)CD27(-) (double negative, DN) and CD21(-)CD11c(+) (CD21(low)) B cells were described as age-associated B cells with proinflammatory characteristics. This study investigated the prevalence and functional characteristics of DN and CD21(low) B cells in multiple sclerosis (MS) patients. Using flow cytometry, we demonstrated a higher proportion of MS patients younger than 60 y with peripheral expansions of DN (8/41) and CD21(low) (9/41) B cells compared with age-matched healthy donors (1/33 and 2/33, respectively), which indicates an increase in age-associated B cells in MS patients...
December 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27819735/hpv-genotype-analysis-for-women-in-shaanxi-province-of-china
#14
J Li, Y Y Wang, X F Tian, X Nan, T Yan, P Wang, Y L Fu, G Q Wang
The aim of this study was to examine the subtype distribution of human papilloma virus (HPV) in women in the Shaanxi Province of China. A DNA chip, along with polymerase chain reaction amplification and reverse dot blot technology, was adopted to analyze the HPV genotypes of 22,937 cases of cervical cell specimens. The HPV infection rate was 18.70%, wherein high-risk, low-risk, and high- and low-risk multiple infection rates were 15.75, 2.96 and 1.91%, respectively. High-risk infections accounted for 84.20% of total infections...
November 3, 2016: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/27814766/antibody-dependent-cd56-t-cell-responses-are-functionally-impaired-in-long-term-hiv-1-infection
#15
Xueying Fan, Liyan Zhu, Hua Liang, Zhe Xie, Xiangbo Huang, Shuo Wang, Tao Shen
BACKGROUND: Antibody-dependent cellular cytotoxicity (ADCC), which mainly mediated by natural killer (NK) cells, may play a critical role in slowing human immunodeficiency virus type-1 (HIV-1) disease progression and protecting from HIV-1 infection. Besides classic NK cells, CD56+ T cells also have some NK cell-like properties, such as the large granular lymphocyte morphology and the capacity to destroy NK-sensitive target cells. However, little is known about the potentials of antibody-dependent CD56+ T cell responses and the association between antibody-dependent CD56+ T cell responses and HIV-1 disease progression...
November 4, 2016: Retrovirology
https://www.readbyqxmd.com/read/27813531/overexpression-of-mcl-1-exacerbates-lymphocyte-accumulation-and-autoimmune-kidney-disease-in-lpr-mice
#16
Natasha S Anstee, Cassandra J Vandenberg, Kirsteen J Campbell, Peter D Hughes, Lorraine A O'Reilly, Suzanne Cory
Cell death by apoptosis has a critical role during embryonic development and in maintaining tissue homeostasis. In mammals, there are two converging apoptosis pathways: the 'extrinsic' pathway, which is triggered by engagement of cell surface 'death receptors' such as Fas/APO-1; and the 'intrinsic' pathway, which is triggered by diverse cellular stresses, and is regulated by pro-survival and pro-apoptotic members of the Bcl-2 family of proteins. Pro-survival Mcl-1, which can block activation of the pro-apoptotic proteins, Bax and Bak, appears critical for the survival and maintenance of multiple haemopoietic cell types...
November 4, 2016: Cell Death and Differentiation
https://www.readbyqxmd.com/read/27810232/potential-role-of-il-17-producing-cd4-cd8-double-negative-%C3%AE-%C3%AE-t-cells-in-psoriatic-skin-inflammation-in-a-tpa-induced-stat3c-transgenic-mouse-model
#17
Azumi Ueyama, Chihiro Imura, Yasuyuki Fusamae, Kenichiro Tsujii, Yoko Furue, Miwa Aoki, Minoru Suzuki, Tomohiko Okuda, Itsuki Oshima, Kiyoshi Yasui, Michitaka Shichijo, Mina Yamamoto
BACKGROUND: Psoriasis is one of the most common immune-mediated chronic inflammatory skin disorders and is accompanied by erythematous scaly plaques. There is growing evidence that the IL-23/Th17 axis plays a critical role in development of the disease. It was recently shown that in addition to CD4(+) Th17 cells, various IL-17-producing cell subsets such as CD8(+) Tc17 cells, dermal γδ T cells, and innate lymphoid cells are also involved in the development of psoriatic inflammation in humans...
October 19, 2016: Journal of Dermatological Science
https://www.readbyqxmd.com/read/27799308/bptf-is-essential-for-t-cell-homeostasis-and-function
#18
Bing Wu, Yunqi Wang, Chaojun Wang, Gang Greg Wang, Jie Wu, Yisong Y Wan
Bromodomain PHD finger transcription factor (BPTF), a ubiquitously expressed ATP-dependent chromatin-remodeling factor, is critical for epigenetically regulating DNA accessibility and gene expression. Although BPTF is important for the development of thymocytes, its function in mature T cells remains largely unknown. By specifically deleting BPTF from late double-negative 3/double-negative 4 stage of developing T cells, we found that BPTF was critical for the homeostasis of T cells via a cell-intrinsic manner...
December 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27797369/association-of-epstein-barr-virus-reactivation-with-the-recovery-of-cd4-cd8-double-negative-t-lymphocytes-after-haploidentical-hematopoietic-stem-cell-transplantation
#19
Z Bian, J Liu, L-P Xu, Y-J Chang, Y Wang, X-H Zhang, X-J Huang
EBV infection is one of the life-threatening clinical complications in patients who underwent haploidentical hematopoietic stem cell transplantation (haploHSCT). Although immune recovery is recognized to be crucial for decreasing subsequent morbidity of infections, the link between T-cell recovery and EBV infection after haploHSCT remains elusive. We recently compared the influences of different doses of antithymocyte globulin conditioning on the T-cell reconstitution post haploHSCT and suggested that CD4(-)CD8(-)T cells might interact with the occurrence of EBV reactivation...
October 31, 2016: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/27784426/-role-of-inhibition-of-nuclear-factor-kappa-b-gene-transcription-by-specific-mirna-in-reversing-multi-drug-resistance-of-liver-cancer
#20
L Wang, Y Cai, Y Shi, M Yao, L H Pan, J J Gu, X L Yang, W Wu, D F Yao
Objective: To investigate the reversal effect of inhibition of nuclear factor-kappa B (NF-κB) gene transcription by specific miRNA on multi-drug resistance (MDR)of liver cancer. Methods: The expression of P-glycoprotein (P-gp) and NF-κB in hepatoma cells, drug-resistant HepG2/ADM cells, and liver cells (LO2 cells) was analyzed. Specific NF-κB miRNA plasmids were constructed, screened, and transfected into HepG2 or HepG2/ADM cells. Western blot was used to measure the concentrations of P-gp and NF-κB, and FQ-PCR was used to measure gene expression; Cell Counting Kit-8 assay was used to measure cell proliferation and the influence of drugs on cell proliferation; flow cytometry and Annexin-V-PE/7-ADD double staining were used to observe cell cycle and apoptosis...
July 20, 2016: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
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