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https://www.readbyqxmd.com/read/28710251/role-for-zap-70-signaling-in-the-differential-effector-functions-of-rituximab-and-obinutuzumab-ga101-in-chronic-lymphocytic-leukemia-b-cells
#1
Sladjana Skopelja-Gardner, Jonathan D Jones, B JoNell Hamilton, Alexey V Danilov, William F C Rigby
Rituximab (RTX) has been the hallmark anti-CD20 mAb for the treatment of B cell neoplasms, including B cell chronic lymphocytic leukemia (B-CLL). Recently, a novel humanized anti-CD20 mAb obinutuzumab (GA101) has been implemented as first-line CLL therapy. Treatment of CLL patients with RTX is associated with CD20 loss via an FcγR-mediated process, trogocytosis. RTX-induced trogocytosis has been characterized as both the means of resistance to therapy, via loss of cell surface target proteins (antigenic modulation), as well as a process that alters B cell phenotype and function...
July 14, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28686740/cd4-cd8-dendritic-cell-complexes-in-the-spleen-cd8-t-cells-can-directly-bind-cd4-t-cells-and-modulate-their-response
#2
Aleksandr Barinov, Alessia Galgano, Gerald Krenn, Corinne Tanchot, Florence Vasseur, Benedita Rocha
CD4+ T cell help to CD8+ T cell responses requires that CD4+ and CD8+ T cells interact with the same antigen presenting dendritic cell (Ag+DC), but it remains controversial whether helper signals are delivered indirectly through a licensed DC and/or involve direct CD4+/CD8+ T cell contacts and/or the formation of ternary complexes. We here describe the first in vivo imaging of the intact spleen, aiming to evaluate the first interactions between antigen-specific CD4+, CD8+ T cells and Ag+DCs. We show that in contrast to CD4+ T cells which form transient contacts with Ag+DC, CD8+ T cells form immediate stable contacts and activate the Ag+DC, acquire fragments of the DC membranes by trogocytosis, leading to their acquisition of some of the DC properties...
2017: PloS One
https://www.readbyqxmd.com/read/28658549/recent-advances-in-understanding-basophil-mediated-th2-immune-responses
#3
REVIEW
Yoshinori Yamanishi, Kensuke Miyake, Misako Iki, Hidemitsu Tsutsui, Hajime Karasuyama
Basophils, the least common granulocytes, represent only ~0.5% of peripheral blood leukocytes. Because of the small number and some similarity with mast cells, the functional significance of basophils remained questionable for a long time. Recent studies using newly-developed analytical tools have revealed crucial and non-redundant roles for basophils in various immune responses, particularly Th2 immunity including allergy and protective immunity against parasitic infections. In this review, we discuss the mechanisms how basophils mediate Th2 immune responses and the nature of basophil-derived factors involved in them...
July 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28656007/association-of-plasmodium-falciparum-with-human-endothelial-cells-in-vitro
#4
Christopher Utter, Adelfa E Serrano, John W Glod, Michael J Leibowitz
Endothelial abnormalities play a critical role in the pathogenesis of malaria caused by the human pathogen, Plasmodium falciparum. In serious infections and especially in cerebral malaria, red blood cells infected with the parasite are sequestered in small venules in various organs, resulting in endothelial activation and vascular occlusion, which are believed to be largely responsible for the morbidity and mortality caused by this infection, especially in children. We demonstrate that after incubation with infected red blood cells (iRBCs), cultured human umbilical vein endothelial cells (HUVECs) contain parasite protein, genomic DNA, and RNA, as well as intracellular vacuoles with apparent parasite-derived material, but not engulfed or adherent iRBCs...
June 2017: Yale Journal of Biology and Medicine
https://www.readbyqxmd.com/read/28585206/adipocyte-macrophage-cross-talk-in-obesity
#5
Ayse Basak Engin
Obesity is characterized by the chronic low-grade activation of the innate immune system. In this respect, macrophage-elicited metabolic inflammation and adipocyte-macrophage interaction has a primary importance in obesity. Large amounts of macrophages are accumulated by different mechanisms in obese adipose tissue. Hypertrophic adipocyte-derived chemotactic monocyte chemoattractant protein-1 (MCP-1)/C-C chemokine receptor 2 (CCR2) pathway also promotes more macrophage accumulation into the obese adipose tissue...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28288980/human-neutrophils-mediate-trogocytosis-rather-than-phagocytosis-of-cll-b-cells-opsonized-with-anti-cd20-antibodies
#6
Rut Valgardsdottir, Irene Cattaneo, Christian Klein, Martino Introna, Marina Figliuzzi, Josée Golay
Polymorphonuclear neutrophils (PMN) have previously been reported to mediate phagocytosis of anti-CD20 opsonized B-cells from CLL patients. However recent data have suggested that PMN, like macrophages, can also mediate trogocytosis. We have performed experiments to more precisely investigate this point and discriminate between trogocytosis and phagocytosis. In live cell time-lapse microscopy experiments, we could not detect any significant phagocytosis by purified PMN of anti-CD20-opsonized CLL B-cells, but only the repeated close contact between effectors and targets, suggesting trogocytosis...
March 13, 2017: Blood
https://www.readbyqxmd.com/read/28255697/plasma-membrane-sheets-for-studies-of-b-cell-antigen-internalization-from-immune-synapses
#7
Carla R Nowosad, Pavel Tolar
Surrogate planar and membrane systems have been employed to study the architecture of immune synapses; however, they often do not recapitulate trans-synaptic extraction and endocytosis of ligands by the immune cells. Transendocytosis (or trogocytosis) of antigen from immune synapses is particularly critical for antigen processing and presentation by B cells. Here we describe a protocol for preparation of plasma membrane sheets (PMSs), which are flexible and fluid membrane substrates that support robust B cell antigen extraction...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28202613/the-activating-human-nk-cell-receptor-kir2ds2-recognizes-a-%C3%AE-2-microglobulin-independent-ligand-on-cancer-cells
#8
Lavanya Thiruchelvam-Kyle, Sigurd E Hoelsbrekken, Per C Saether, Elisabeth Gyllensten Bjørnsen, Daniela Pende, Sigbjørn Fossum, Michael R Daws, Erik Dissen
The functions of activating members of the killer cell Ig-like receptor (KIR) family are not fully understood, as the ligands for these receptors are largely unidentified. In this study, we report that KIR2DS2 reporter cells recognize a ligand expressed by cancer cell lines. All cancer targets recognized by KIR2DS2 were also recognized by KIR2DL2 and KIR2DL3 reporters. Trogocytosis of membrane proteins from the cancer targets was observed with responding reporter cells, indicating the formation of KIR2DS2 ligand-specific immunological synapses...
April 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28118592/embryonic-trogocytosis-neighborly-nibbling-during-development
#9
Justin S A Perry, Kodi S Ravichandran
New work in Caenorhabditis elegans shows that during embryogenesis endodermal cells interact with and regulate primordial germ cells by actively excising and digesting germ cell lobes. Endodermal cells utilize proteins linked to endocytosis to perform this unique 'cannibalistic' process.
January 23, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28096423/trogocytosis-of-peptide-mhc-class-ii-complexes-from-dendritic-cells-confers-antigen-presenting-ability-on-basophils
#10
Kensuke Miyake, Nozomu Shiozawa, Toshihisa Nagao, Soichiro Yoshikawa, Yoshinori Yamanishi, Hajime Karasuyama
Th2 immunity plays important roles in both protective and allergic responses. Nevertheless, the nature of antigen-presenting cells responsible for Th2 cell differentiation remains ill-defined compared with the nature of the cells responsible for Th1 and Th17 cell differentiation. Basophils have attracted attention as a producer of Th2-inducing cytokine IL-4, whereas their MHC class II (MHC-II) expression and function as antigen-presenting cells are matters of considerable controversy. Here we revisited the MHC-II expression on basophils and explored its functional relevance in Th2 cell differentiation...
January 31, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27601001/the-t-cell-in-myeloma
#11
Douglas Joshua, Hayley Suen, Ross Brown, Christian Bryant, P Joy Ho, Derek Hart, John Gibson
An active role for the immune system in controlling the malignant plasma cell clone in myeloma has been postulated for many years. The clinical states of monoclonal gammopathy of undetermined significance, plateau phase disease, and smoldering myeloma all suggest that a significant host-tumor interaction is taking place. The fundamental role of the cytotoxic T cell in tumor elimination and control has been exemplified by the dramatic efficacy of adoptive T-cell therapies in many hemopoietic malignancies. However, tumor-host cross-talk results in suppression of the endogenous cytotoxic T-cell response against the malignant plasma cell...
August 10, 2016: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/27554051/contribution-of-fc%C3%A9-ri-associated-vesicles-to-mast-cell-macrophage-communication-following-francisella-tularensis-infection
#12
Annette R Rodriguez, Jieh-Juen Yu, Christopher Navara, James P Chambers, M Neal Guentzel, Bernard P Arulanandam
Understanding innate immune intercellular communication following microbial infection remains a key biological issue. Using live cell imaging, we demonstrate that mast cells actively extend cellular projections to sample the macrophage periphery during Francisella tularensis LVS infection. Mast cell MHCII(hi) expression was elevated from less than 1% to 13% during LVS infection. Direct contact during co-culture with macrophages further increased mast cell MHCII(hi) expression to approximately 87%. Confocal analyses of the cellular perimeter revealed mast cell caspase-1 was localized in close proximity with FcɛRI in uninfected mast cells, and repositioned to clustered regions upon LVS infection...
October 2016: Innate Immunity
https://www.readbyqxmd.com/read/27430580/targeting-kir-blockade-in-multiple-myeloma-trouble-in-checkpoint-paradise
#13
Martin Felices, Jeffrey S Miller
Findings within the current issue indicate that treatment with IPH2101 when used as a monotherapy in smoldering multiple myeloma, meant to enhance natural killer (NK) cell function through inhibitory KIR blockade, results in a surprising reduction of NK-cell function mediated through monocyte trogocytosis. The significance of these findings is discussed. Clin Cancer Res; 22(21); 5161-3. ©2016 AACRSee related article by Carlsten et al., p. 5211.
November 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27307594/checkpoint-inhibition-of-kir2d-with-the-monoclonal-antibody-iph2101-induces-contraction-and-hyporesponsiveness-of-nk-cells-in-patients-with-myeloma
#14
Mattias Carlsten, Neha Korde, Ritesh Kotecha, Robert Reger, Simona Bor, Dickran Kazandjian, Ola Landgren, Richard W Childs
PURPOSE: Immune checkpoint inhibitors have recently revolutionized cancer immunotherapy. On the basis of data showing KIR-ligand mismatched natural killer (NK) cells reduce the risk of leukemia and multiple myeloma relapse following allogeneic hematopoietic stem cell transplantation, investigators have developed a checkpoint inhibition antibody that blocks KIR on NK cells. Although in vitro studies suggest the KIR2D-specific antibody IPH2101 induces KIR-ligand mismatched tumor killing by NK cells, our single-arm phase II clinical trial in patients with smoldering multiple myeloma was prematurely terminated due to lack of clinical efficacy...
November 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27258015/membrane-transfer-from-mononuclear-cells-to-polymorphonuclear-neutrophils-transduces-cell-survival-and-activation-signals-in-the-recipient-cells-via-anti-extrinsic-apoptotic-and-map-kinase-signaling-pathways
#15
Ko-Jen Li, Cheng-Han Wu, Chieh-Yu Shen, Yu-Min Kuo, Chia-Li Yu, Song-Chou Hsieh
The biological significance of membrane transfer (trogocytosis) between polymorphonuclear neutrophils (PMNs) and mononuclear cells (MNCs) remains unclear. We investigated the biological/immunological effects and molecular basis of trogocytosis among various immune cells in healthy individuals and patients with active systemic lupus erythematosus (SLE). By flow cytometry, we determined that molecules in the immunological synapse, including HLA class-I and-II, CD11b and LFA-1, along with CXCR1, are exchanged among autologous PMNs, CD4+ T cells, and U937 cells (monocytes) after cell-cell contact...
2016: PloS One
https://www.readbyqxmd.com/read/27226489/macrophage-mediated-trogocytosis-leads-to-death-of-antibody-opsonized-tumor-cells
#16
Ramraj Velmurugan, Dilip K Challa, Sripad Ram, Raimund J Ober, E Sally Ward
Understanding the complex behavior of effector cells such as monocytes or macrophages in regulating cancerous growth is of central importance for cancer immunotherapy. Earlier studies using CD20-specific antibodies have demonstrated that the Fcγ receptor (FcγR)-mediated transfer of the targeted receptors from tumor cells to these effector cells through trogocytosis can enable escape from antibody therapy, leading to the viewpoint that this process is protumorigenic. In the current study, we demonstrate that persistent trogocytic attack results in the killing of HER2-overexpressing breast cancer cells...
August 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27177672/engineering-receptor-expression-on-natural-killer-cells-through-trogocytosis
#17
Anitha Somanchi, Dean A Lee, Srinivas S Somanchi
Trogocytosis is a rapid contact-dependent process by which lymphocytes acquire membrane patches from the target cells ('donor' cells) with which they interact and this phenomenon has been shown to occur in various immune cells. The surface molecules acquired through trogocytosis are functionally incorporated in the 'acceptor' cells transiently. We had previously demonstrated that trogocytosis can be utilized in place of gene transfer to engineer surface receptor expression on NK cells for adoptive immunotherapy applications...
2016: Methods in Molecular Biology
https://www.readbyqxmd.com/read/26994325/new-perspectives-on-complement-mediated-immunotherapy
#18
REVIEW
Grzegorz Stasiłojć, Anders Österborg, Anna M Blom, Marcin Okrój
Tumor-specific monoclonal antibodies (mAbs) offer several modes of tumor cell killing, from direct cytotoxic activity to indirect mechanisms employing the host immune system, particularly its innate branch. The latter effector functions seem to dominate among clinically approved anti-cancer mAbs and major efforts are being undertaken by both academia and the pharmaceutical industry with the aim to improve complement activation, antibody-dependent cellular cytotoxicity (ADCC) and Fc/opsonin-mediated phagocytosis...
April 2016: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/26802627/trogocytosis-associated-cell-to-cell-spread-of-intracellular-bacterial-pathogens
#19
Shaun Steele, Lauren Radlinski, Sharon Taft-Benz, Jason Brunton, Thomas H Kawula
Macrophages are myeloid-derived phagocytic cells and one of the first immune cell types to respond to microbial infections. However, a number of bacterial pathogens are resistant to the antimicrobial activities of macrophages and can grow within these cells. Macrophages have other immune surveillance roles including the acquisition of cytosolic components from multiple types of cells. We hypothesized that intracellular pathogens that can replicate within macrophages could also exploit cytosolic transfer to facilitate bacterial spread...
January 23, 2016: ELife
https://www.readbyqxmd.com/read/26629531/identification-of-anti-tumor-cells-carrying-natural-killer-nk-cell-antigens-in-patients-with-hematological-cancers
#20
Ewelina Krzywinska, Nerea Allende-Vega, Amelie Cornillon, Dang-Nghiem Vo, Laure Cayrefourcq, Catherine Panabieres, Carlos Vilches, Julie Déchanet-Merville, Yosr Hicheri, Jean-François Rossi, Guillaume Cartron, Martin Villalba
Natural killer (NK) cells, a cytotoxic lymphocyte lineage, are able to kill tumor cells in vitro and in mouse models. However, whether these cells display an anti-tumor activity in cancer patients has not been demonstrated. Here we have addressed this issue in patients with several hematological cancers. We found a population of highly activated CD56(dim)CD16(+) NK cells that have recently degranulated, evidence of killing activity, and it is absent in healthy donors. A high percentage of these cells expressed natural killer cell p46-related protein (NKp46), natural-killer group 2, member D (NKG2D) and killer inhibitory receptors (KIRs) and a low percentage expressed NKG2A and CD94...
October 2015: EBioMedicine
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