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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
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
Martin Felices, Jeffrey S Miller
Findings within the current issue indicate that treatment with IPH2101 when used as monotherapy in smoldering multiple myeloma, meant to enhance natural killer 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.
July 18, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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. Based on data showing KIR-ligand mismatched NK-cells reduce the risk of leukemia and multiple myeloma (MM) 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 MM was prematurely terminated due to lack of clinical efficacy...
June 15, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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
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
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
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
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...
2016: ELife
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
Tamara Tilburgs, J Henry Evans, Ângela C Crespo, Jack L Strominger
The interaction of noncytotoxic decidual natural killer cells (dNK) and extravillous trophoblasts (EVT) at the maternal-fetal interface was studied. Confocal microscopy revealed that many dNK interact with a single large EVT. Filamentous projections from EVT enriched in HLA-G were shown to contact dNK, and may represent the initial stage of synapse formation. As isolated, 2.5% of dNK contained surface HLA-G. However, surface HLA-G-negative dNK contained internalized HLA-G. Activation of dNK resulted in the disappearance of internalized HLA-G in parallel with restoration of cytotoxicity...
October 27, 2015: Proceedings of the National Academy of Sciences of the United States of America
Yekaterina O Ostapchuk, Esin Aktas Cetin, Yuliya V Perfilyeva, Abdullah Yilmaz, Yuriy A Skiba, Alexandr P Chirkin, Nazgul A Omarbaeva, Shynar G Talaeva, Nikolai N Belyaev, Gunnur Deniz
Human natural killer (NK) cells are not only professional cytotoxic cells integrated into effector branch of innate immunity, but they are also regulatory cells, managing different immune processes. Immunoregulatory NK cells, expressing HLA-G and IL-10, have been generated in vitro from human hematopoietic progenitors and found in vivo among decidual NK cells of pregnant women. Human peripheral blood NK cells have been shown to acquire suppressive properties after HLA-G uptake during trogocytosis. Moreover, it has been shown that circulating NK cells contain a trace amount of cells producing TGF-β and IL-10, which exert a suppressive influence upon innate and adaptive immunity...
November 2015: Cellular Immunology
Martin Skarzynski, Carsten U Niemann, Yuh Shan Lee, Sabrina Martyr, Irina Maric, Dalia Salem, Maryalice Stetler-Stevenson, Gerald E Marti, Katherine R Calvo, Constance Yuan, Janet Valdez, Susan Soto, Mohammed Z H Farooqui, Sarah E M Herman, Adrian Wiestner
PURPOSE: Clinical trials of ibrutinib combined with anti-CD20 monoclonal antibodies (mAb) for chronic lymphocytic leukemia (CLL) report encouraging results. Paradoxically, in preclinical studies, in vitro ibrutinib was reported to decrease CD20 expression and inhibit cellular effector mechanisms. We therefore set out to investigate effects of in vivo ibrutinib treatment that could explain this paradox. EXPERIMENTAL DESIGN: Patients received single-agent ibrutinib (420 mg daily) on an investigator-initiated phase II trial...
January 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Katherine S Ralston
Entamoeba histolytica is a diarrheal pathogen with the ability to cause profound host tissue damage. This organism possesses contact-dependent cell killing activity, which is likely to be a major contributor to tissue damage. E. histolytica trophozoites were recently shown to ingest fragments of living human cells. It was demonstrated that this process, termed amoebic trogocytosis, contributes to cell killing. Recent advances in ex vivo and 3-D cell culture approaches have shed light on mechanisms for tissue destruction by E...
December 2015: Current Opinion in Microbiology
Laura Amo, Estíbaliz Tamayo-Orbegozo, Natalia Maruri, Aitziber Buqué, Miren Solaun, Marta Riñón, Arantza Arrieta, Susana Larrucea
Podocalyxin-like protein 1 (PCLP1), a CD34-related sialomucin involved in the regulation of cellular morphology and adhesion, is expressed by a number of normal cells and various tumor cells. In breast malignancies PCLP1 overexpression has been associated with the most aggressive, metastatic cancers and poor prognosis. These observations suggest that PCLP1 expression could provide a mechanism to evade the immune response, thereby promoting metastatic progression of cancer. In the present work, we aimed to determine the effect of PCLP1 overexpressed in MCF7 breast cancer cells on natural killer (NK) cell cytotoxicity, dendritic cell maturation, and agonist-induced T cell proliferation...
November 1, 2015: Cancer Letters
Marco de Bruyn, Valerie R Wiersma, Maartje C A Wouters, Douwe F Samplonius, Harry G Klip, Wijnand Helfrich, Hans W Nijman, Paul Eggleton, Edwin Bremer
Recently, a small subset of T cells that expresses the B cell marker CD20 has been identified in healthy volunteers and in patients with rheumatoid arthritis and multiple sclerosis. The origin of these CD20-positive T cells as well as their relevance in human disease remains unclear. Here, we identified that after functional B cell/T cell interaction CD20 molecules are transferred to the cell surface of T cells by trogocytosis together with the established trogocytosis marker HLA-DR. Further, the presence of CD20 on isolated CD20(+) T cells remained stable for up to 48h of ex vivo culture...
April 2015: Oncoimmunology
Katherine S Ralston
Entamoeba histolytica was named 'histolytica' (from histo-, 'tissue'; lytic-, 'dissolving') for its ability to destroy host tissues. Direct killing of host cells by the amoebae is likely to be the driving factor that underlies tissue destruction, but the mechanism was unclear. We recently showed that, after attaching to host cells, amoebae bite off and ingest distinct host cell fragments, and that this contributes to cell killing. We review this process, termed 'amoebic trogocytosis' (trogo-, 'nibble'), and how this process interplays with phagocytosis, or whole cell ingestion, in this organism...
September 2015: Trends in Parasitology
Silvia Pesce, Simona Carlomagno, Alessandro Moretta, Simona Sivori, Emanuela Marcenaro
The KIR2DS4 receptor is the oldest KIR2DS expressed by human NK lymphocytes. The specificity of recognition of this receptor for various HLA class I alleles has been demonstrated; however it remains poorly understood whether these interactions may result in the activation of some specific functions in NK cells. Here, we examined the functional outcome of the KIR2DS4/HLA class I interaction by the use of an alternative functional system based on the ability of KIR2DS4 to regulate the mechanism of trogocytosis by NK cells...
2015: Journal of Immunology Research
Inge M Werter, Famke L Schneiders, Emmanuel Scotet, Henk M W Verheul, Tanja D de Gruijl, Hans J van der Vliet
CD1d-restricted invariant natural killer T cells (iNKT) constitute an important immunoregulatory T-cell subset involved in the induction of antitumor immune responses. Here, we provide a view on the recent observation that Vγ9Vδ2-T cells, through trogocytosis of CD1d-containing membrane fragments, have the capacity to act as antigen presenting cells for iNKT.
October 2014: Oncoimmunology
Alicja Trzeciak-Ryczek, Beata Tokarz-Deptuła, Wiesław Deptuła
Fungi are omnipresent in the environment; hence they are frequent factors causing infections in humans and animals even if their immune system works correctly. These facts stimulated interest in and the will to understand the antifungal immunity mechanisms. It has been, however, evidenced that the immunological response to mycotic pathogens is related to the species and morphological form of the fungus. Nevertheless, it is assumed that always in the antifungal response, there are mechanisms of innate and adaptive immunity that cooperate with one another to eliminate such pathogens...
2015: Postȩpy Higieny i Medycyny Doświadczalnej
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