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Tumor immune recognition

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https://www.readbyqxmd.com/read/29232467/immunotherapy-in-ovarian-cancer
#1
K Odunsi
Immunological destruction of tumors is a multistep, coordinated process that can be modulated or targeted at several critical points to elicit tumor rejection. These steps in the cancer immunity cycle include: (i) generation of sufficient numbers of effector T cells with high avidity recognition of tumor antigens in vivo; (ii) trafficking and infiltration into the tumor; (iii) overcoming inhibitory networks in the tumor microenvironment; (iv) direct recognition of tumor antigens and generation of an effector anti-tumor response; and (v) persistence of the anti-tumor T cells...
November 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29229677/apoptotic-cancer-cells-suppress-5-lipoxygenase-in-tumor-associated-macrophages
#2
Julia Ringleb, Elisabeth Strack, Carlo Angioni, Gerd Geisslinger, Dieter Steinhilber, Andreas Weigert, Bernhard Brüne
The enzyme 5-lipoxygenase (5-LO) is key in the synthesis of leukotrienes, which are potent proinflammatory lipid mediators involved in chronic inflammatory diseases including cancer. 5-LO is expressed in immune cells but also found in cancer cells. Although the role of 5-LO in tumor cells is beginning to emerge, with the notion that tumor-promoting functions are attributed to its products, the function of 5-LO in the tumor microenvironment remains unclear. To understand the role of 5-LO and its products in the tumor microenvironment, we analyzed its expression and function in tumor-associated macrophages (TAMs)...
December 11, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29224886/-spheroids-a-reference-model-for-in-vitro-culture-of-solid-tumors
#3
REVIEW
Christian-Jacques Larsen
The recognition that solid tumors are complex entities composed of the tumor cell mass itself and a stromal micro-environnement providing a variety of cells from the host (fibroblasts, endothelial cells, immune cells) led to recognize that this heterogeneity could not be recapitulated in vitro by conventional bidimensional (2-D) cultures. This justified numerous attempts to develop tridimensional (3-D) cultures that provided better tools for approaching tumor complexity and more convincing drug testing systems...
December 7, 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/29222323/graft-versus-tumor-effects-and-why-people-relapse
#4
REVIEW
J H Frederik Falkenburg, Inge Jedema
Graft-versus-tumor (GVT) reactivity mediated by donor T cells in the context of allogeneic stem cell transplantation (alloSCT) is one of the most potent forms of cellular immunotherapy. The antitumor effect against hematologic malignancies is mediated by a polyclonal T-cell response targeting polymorphic antigens expressed on hematopoietic tissues of the recipient, leaving donor hematopoiesis in the patient after transplantation unharmed. Fortunately, hematopoietic tissues (including malignant hematopoietic cell populations) are relatively susceptible to T-cell recognition...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29221220/significant-benefit-of-nivolumab-treating-pd-l1-positive-metastatic-pulmonary-carcinosarcoma-a-case-report-and-literature-review
#5
Zhe Zhang, Yishan Chen, Mingxia Ma, Junli Hao, Rui Ding, Lixin Han, Jiayun Zou, Lina Zhang, Qin Meng, Xiujuan Qu, Yunpeng Liu, Mingfang Zhao
Immunotherapy has recently become a new focus for the treatment of malignant tumors following the surgery, chemotherapy, radiotherapy, and molecular targeted therapy. Nivolumab, a human monoclonal antibody, is the first programmed cell death protein-1 (PD-1) inhibitor, which can prohibit the interaction of its ligand (PD-L1), restoring the immune response of T cells, and enhancing the recognition of tumor cells by the immune system. Pulmonary carcinosarcoma is an uncommon but highly aggressive tumor type with a poor prognosis...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29217585/patient-hla-class-i-genotype-influences-cancer-response-to-checkpoint-blockade-immunotherapy
#6
Diego Chowell, Luc G T Morris, Claud M Grigg, Jeffrey K Weber, Robert M Samstein, Vladimir Makarov, Fengshen Kuo, Sviatoslav M Kendall, David Requena, Nadeem Riaz, Benjamin Greenbaum, James Carroll, Edward Garon, David M Hyman, Ahmet Zehir, David Solit, Michael Berger, Ruhong Zhou, Naiyer A Rizvi, Timothy A Chan
CD8+ T cell-dependent killing of cancer cells requires efficient presentation of tumor antigens by human leukocyte antigen class I (HLA-I) molecules. However, the extent to which patient-specific HLA-I genotype influences response to anti-PD-1 or anti-CTLA-4 is currently unknown. We determined the HLA-I genotype of 1,535 advanced cancer patients treated with immune checkpoint blockade (ICB). Maximal heterozygosity at HLA-I loci (A, B, and C) improved overall survival after ICB compared to patients who were homozygous for at least one HLA locus...
December 7, 2017: Science
https://www.readbyqxmd.com/read/29211501/viral-subversion-of-apobec3s-lessons-for-anti-tumor-immunity-and-tumor-immunotherapy
#7
Faezeh Borzooee, Mahdi Asgharpour, Emma Quinlan, Michael D Grant, Mani Larijani
APOBEC3s (A3) are endogenous DNA-editing enzymes that are expressed in immune cells including T lymphocytes. A3s target and mutate the genomes of retroviruses that infect immune tissues such as the human immunodeficiency virus (HIV). Therefore, A3s were classically defined as host anti-viral innate immune factors. In contrast, we and others showed that A3s can also benefit the virus by mediating escape from adaptive immune recognition and drugs. Crucially, whether A3-mediated mutations help or hinder HIV, is not up to chance...
December 6, 2017: International Reviews of Immunology
https://www.readbyqxmd.com/read/29209316/complement-protein-c1q-binds-to-hyaluronic-acid-in-the-malignant-pleural-mesothelioma-microenvironment-and-promotes-tumor-growth
#8
Chiara Agostinis, Romana Vidergar, Beatrice Belmonte, Alessandro Mangogna, Leonardo Amadio, Pietro Geri, Violetta Borelli, Fabrizio Zanconati, Francesco Tedesco, Marco Confalonieri, Claudio Tripodo, Uday Kishore, Roberta Bulla
C1q is the first recognition subcomponent of the complement classical pathway, which acts toward the clearance of pathogens and apoptotic cells. C1q is also known to modulate a range of functions of immune and non-immune cells, and has been shown to be involved in placental development and sensorial synaptic pruning. We have recently shown that C1q can promote tumor by encouraging their adhesion, migration, and proliferation in addition to angiogenesis and metastasis. In this study, we have examined the role of human C1q in the microenvironment of malignant pleural mesothelioma (MPM), a rare form of cancer commonly associated with exposure to asbestos...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29198976/ligand-free-method-to-produce-the-anti-angiogenic-recombinant-galectin-3-carbohydrate-recognition-domain
#9
Adalgisa Wiecikowski, Katia Maria Dos Santos Cabral, Marcius da Silva Almeida, Renato Sampaio Carvalho
Galectin-3 (Gal3) is involved in many physiological processes related to tumor growth, such as promoting angiogenesis, cell migration/invasion, resistance to apoptosis and immune response modulation. Usually the overexpression of Gal3 is a poor prognostic marker for cancer patients. Recombinant Gal3 carbohydrate domain (Gal3C) has been proposed as a useful tool to inhibit angiogenesis. So far, all production protocols reported for Gal3C production have used proteolytic cleavage of full length Gal3 and/or affinity-based purification...
November 30, 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/29198314/t-cell-resistance-to-activation-by-dendritic-cells-requires-long-term-culture-in-simulated-microgravity
#10
Jillian H Bradley, Rachel Stein, Brad Randolph, Emily Molina, Jennifer P Arnold, Randal K Gregg
Immune impairment mediated by microgravity threatens the success of space exploration requiring long-duration spaceflight. The cells of most concern, T lymphocytes, coordinate the host response against microbial and cancerous challenges leading to elimination and long-term protection. T cells are activated upon recognition of specific microbial peptides bound on the surface of antigen presenting cells, such as dendritic cells (DC). Subsequently, this engagement results in T cell proliferation and differentiation into effector T cells driven by autocrine interleukin-2 (IL-2) and other cytokines...
November 2017: Life Sciences in Space Research
https://www.readbyqxmd.com/read/29188488/lipopolysaccharide-induced-microglia-activation-promotes-the-survival-of-midbrain-dopaminergic-neurons-in-vitro
#11
Xiaolai Zhou, Björn Spittau
Microglia are the resident immune cells of the central nervous system (CNS) and respond to a variety of endogenous and exogenous stimuli in order to restore cell and tissue homeostasis. Lipopolysaccharide (LPS) is one of these exogenous stimuli, constitutes a major component of the outer membrane of Gram-negative bacteria, and binds to the microglial pattern recognition receptor Toll-like receptor 4 (TLR4). LPS-induced microglia activation is believed to promote neurodegeneration by release of neurotoxic factors such as interleukin-1β, tumor necrosis factor α, or nitric oxide...
November 29, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/29183999/autopolysialylation-of-polysialyltransferases-is-required-for-polysialylation-and-polysialic-acid-chain-elongation-on-select-glycoprotein-substrates
#12
Gaurang P Bhide, Joseph L Zapater, Karen J Colley
Polysialic acid (polySia) is a large glycan polymer that is added to some glycoproteins by two polysialyltransferases (polySTs), ST8Sia-II and ST8Sia-IV. As polySia modulates cell adhesion and signaling, immune cell function, and tumor metastasis, it is of interest to determine how the polySTs recognize their select substrates. We have recently identified residues within the ST8Sia-IV polybasic region (PBR) that are required for neural cell adhesion molecule (NCAM) recognition and subsequent polysialylation...
November 28, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29175552/long-pentraxin-3-a-novel-multifaceted-player-in-cancer
#13
REVIEW
Arianna Giacomini, Gaia Cristina Ghedini, Marco Presta, Roberto Ronca
Since its discovery in 1992, long pentraxin 3 (PTX3) has been characterized as soluble patter recognition receptor, a key player of the innate immunity arm with non-redundant functions in pathogen recognition and inflammatory responses. As a component of the extra-cellular matrix milieu, PTX3 has been implicated also in wound healing/tissue remodeling, cardiovascular diseases, fertility, and infectious diseases. Consequently, PTX3 levels in biological fluids have been proposed as a fluid-phase biomarker in different pathological conditions...
November 23, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29175315/flagellin-increases-death-receptor-mediated-cell-death-in-a-rip1-dependent-manner
#14
Dora Hancz, Aniko Szabo, Tamás Molnar, Zsofia Varga, Aniko Hancz, Andrea Gregus, Anne-Odile Hueber, Eva Rajnavolgyi, Gabor Koncz
Efficient adjuvants have the potential to trigger both innate and adaptive immune responses simultaneously. Flagellin is a unique pathogen-derived protein, which is recognized by pattern recognition receptors (PRRs) as well as by B-cell and T cell receptors thus providing an important link between innate and adaptive immunity. The aforementioned properties define flagellin as an optimal adjuvant. The induction of immunogenic cell death could be an additional expectation for adjuvants in the context of cancer immunotherapy due to their ability to activate dendritic cells (DC) to present tumor antigens through the engulfment of dying cells...
November 22, 2017: Immunology Letters
https://www.readbyqxmd.com/read/29169777/one-step-fplc-size-exclusion-chromatography-procedure-for-purification-of-rdmbt1-6%C3%A2-kb-with-increased-biological-activity
#15
Martina Tuttolomondo, Pernille Lund Hansen, Jan Mollenhauer, Henrik J Ditzel
Deleted in Malignant Brain Tumor 1 (DMBT1, alias SAG or gp340) is a pattern recognition receptor involved in immune defense, cell polarization, differentiation and regeneration. To investigate the role of the protein in physiological and pathological processes, the protein has often been isolated from saliva or produced in vitro and purified by a multistep affinity purification procedure using bacteria, followed by FPLC. Here, we compared a simple, one-step FPLC-SEC protocol for purification of recombinant DMBT1 6 kb, with that of the standard bacteria affinity purification-based protocol...
November 20, 2017: Analytical Biochemistry
https://www.readbyqxmd.com/read/29163516/restoring-natural-killer-cell-immunity-against-multiple-myeloma-in-the-era-of-new-drugs
#16
REVIEW
Gianfranco Pittari, Luca Vago, Moreno Festuccia, Chiara Bonini, Deena Mudawi, Luisa Giaccone, Benedetto Bruno
Transformed plasma cells in multiple myeloma (MM) are susceptible to natural killer (NK) cell-mediated killing via engagement of tumor ligands for NK activating receptors or "missing-self" recognition. Similar to other cancers, MM targets may elude NK cell immunosurveillance by reprogramming tumor microenvironment and editing cell surface antigen repertoire. Along disease continuum, these effects collectively result in a progressive decline of NK cell immunity, a phenomenon increasingly recognized as a critical determinant of MM progression...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29155844/hypoxia-and-hypoxia-inducible-factor-hif-downregulate-antigen-presenting-mhc-class-i-molecules-limiting-tumor-cell-recognition-by-t-cells
#17
Shalini Sethumadhavan, Murillo Silva, Phaethon Philbrook, Thao Nguyen, Stephen M Hatfield, Akio Ohta, Michail V Sitkovsky
Human cancers are known to downregulate Major Histocompatibility Complex (MHC) class I expression thereby escaping recognition and rejection by anti-tumor T cells. Here we report that oxygen tension in the tumor microenvironment (TME) serves as an extrinsic cue that regulates antigen presentation by MHC class I molecules. In support of this view, hypoxia is shown to negatively regulate MHC expression in a HIF-dependent manner as evidenced by (i) lower MHC expression in the hypoxic TME in vivo and in hypoxic 3-dimensional (3D) but not 2-dimensional (2D) tumor cell cultures in vitro; (ii) decreased MHC in human renal cell carcinomas with constitutive expression of HIF due to genetic loss of von Hippel-Lindau (VHL) function as compared with isogenically paired cells with restored VHL function, and iii) increased MHC in tumor cells with siRNA-mediated knockdown of HIF...
2017: PloS One
https://www.readbyqxmd.com/read/29150600/mapping-tenascin-c-interaction-with-toll-like-receptor-4-reveals-a-new-subset-of-endogenous-inflammatory-triggers
#18
Lorena Zuliani-Alvarez, Anna M Marzeda, Claire Deligne, Anja Schwenzer, Fiona E McCann, Brian D Marsden, Anna M Piccinini, Kim S Midwood
Pattern recognition underpins innate immunity; the accurate identification of danger, including infection, injury, or tumor, is key to an appropriately targeted immune response. Pathogen detection is increasingly well defined mechanistically, but the discrimination of endogenous inflammatory triggers remains unclear. Tenascin-C, a matrix protein induced upon tissue damage and expressed by tumors, activates toll-like receptor 4 (TLR4)-mediated sterile inflammation. Here we map three sites within tenascin-C that directly and cooperatively interact with TLR4...
November 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/29147609/tumor-immunology-meets%C3%A2-immunology-modified-cancer-cells-as-professional-apc-for-priming-na%C3%A3-ve-tumor-specific-cd4-t-cells
#19
REVIEW
Farah Bou Nasser Eddine, Elise Ramia, Giovanna Tosi, Greta Forlani, Roberto S Accolla
Although recent therapeutic approaches have revitalized the enthusiasm of the immunological way to combat cancer, still the comprehension of immunity against tumors is largely incomplete. Due to their specific function, CD8+ T cells with cytolytic activity (CTL) have attracted the attention of most investigators because CTL are considered the main effectors against tumor cells. Nevertheless, CTL activity and persistence is largely dependent on the action of CD4+ T helper cells (TH). Thus establishment of tumor-specific TH cell response is key to the optimal response against cancer...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29145317/complete-remission-and-long-term-survival-of-a-patient-with-melanoma-metastases-treated-with-high-dose-fever-inducing-viscum-album-extract-a-case-report
#20
Paul G Werthmann, Alexander Hintze, Gunver S Kienle
INTRODUCTION: Metastatic malignant cutaneous melanoma (MCM)-a highly immunogenic cancer-typically has a poor prognosis. Viscum album extracts (VAEs) have strong immune-stimulating, apoptogenic, and cytotoxic effects. CASE PRESENTATION: A 66-year-old MCM patient with newly diagnosed lymph node metastases opted for sole VAE treatment. VAEs were initially applied subcutaneously, and then later in exceptionally high, fever-inducing doses, both intravenously and intralesionally...
November 2017: Medicine (Baltimore)
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