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Combined immunotherapy

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https://www.readbyqxmd.com/read/29678874/mitochondrial-morphological-and-functional-reprogramming-following-cd137-4-1bb-co-stimulation
#1
Alvaro Teijeira, Sara Labiano, Saray Garasa, Inaki Etxeberria, Eva Santamaria, Ana Rouzaut, Michel Enamorado, Arantza Azpilikueta, Susana Inoges, Elixabet Bolanos-Mateo, Maria Angela Aznar, Alfonso R Sanchez-Paulete, David Sancho, Ignacio Melero
T and NK lymphocytes express CD137 (4-1BB), a costimulatory receptor of the TNFR family whose function is exploitable for cancer immunotherapy. Mitochondria regulate the function and survival of T lymphocytes. Herein, we show that CD137 costimulation provided by agonist mAb and CD137L (4-1BBL) induced mitochondria enlargement that resulted in enhanced mitochondrial mass and transmembrane potential in human and mouse CD8+ T cells. Such mitochondrial changes increased T-cell respiratory capacities and were critically dependent on mitochondrial fusion protein OPA-1 expression...
April 20, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29676439/oral-and-sublingual-immunotherapy-for-egg-allergy
#2
REVIEW
Olga Romantsik, Maria Angela Tosca, Simona Zappettini, Maria Grazia Calevo
BACKGROUND: Clinical egg allergy is a common food allergy. Current management relies upon strict allergen avoidance. Oral immunotherapy might be an optional treatment, through desensitization to egg allergen. OBJECTIVES: To determine the efficacy and safety of oral and sublingual immunotherapy in children and adults with immunoglobulin E (IgE)-mediated egg allergy as compared to a placebo treatment or an avoidance strategy. SEARCH METHODS: We searched 13 databases for journal articles, conference proceedings, theses and trials registers using a combination of subject headings and text words (last search 31 March 2017)...
April 20, 2018: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/29676175/epigenetic-agents-in-combined-anticancer-therapy
#3
Zdeněk Kejík, Milan Jakubek, Robert Kaplánek, Jarmila Králová, Ivan Mikula, Pavel Martásek, Vladimír Král
In the last decade, epigenetic drugs (such as inhibitors of DNA methyltransferases and histone deacetylases) have been intensively used for cancer treatment. Their applications have shown high anticancer effectivity and tolerable side effects. However, they are unfortunately not effective in the treatment of some types and phenotypes of cancers. Nevertheless, several studies have demonstrated that problems of drug efficacy can be overcome through the combined application of therapeutic modulates. Therefore, combined applications of epigenetic agents with chemotherapy, radiation therapy, immunotherapy, oncolytic virotherapy and hyperthermia have been presented...
April 20, 2018: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/29676066/allergen-specific-immunotherapies-for-food-allergy
#4
REVIEW
Elizabeth Feuille, Anna Nowak-Wegrzyn
With rising prevalence of food allergy (FA), allergen-specific immunotherapy (AIT) for FA has become an active area of research in recent years. In AIT, incrementally increasing doses of inciting allergen are given with the goal to increase tolerance, initially through desensitization, which relies on regular exposure to allergen. With prolonged therapy in some subjects, AIT may induce sustained unresponsiveness, in which tolerance is retained after a period of allergen avoidance. Methods of AIT currently under study in humans include oral, sublingual, epicutaneous, and subcutaneous delivery of modified allergenic protein, as well as via DNA-based vaccines encoding allergen with lysosomal-associated membrane protein I...
May 2018: Allergy, Asthma & Immunology Research
https://www.readbyqxmd.com/read/29675465/elimination-of-established-tumors-with-nanodisc-based-combination-chemoimmunotherapy
#5
Rui Kuai, Wenmin Yuan, Sejin Son, Jutaek Nam, Yao Xu, Yuchen Fan, Anna Schwendeman, James J Moon
Although immune checkpoint blockade has shown initial success for various cancers, only a small subset of patients benefits from this therapy. Some chemotherapeutic drugs have been reported to induce antitumor T cell responses, prompting a number of clinical trials on combination chemoimmunotherapy. However, how to achieve potent immune activation with traditional chemotherapeutics in a manner that is safe, effective, and compatible with immunotherapy remains unclear. We show that high-density lipoprotein-mimicking nanodiscs loaded with doxorubicin (DOX), a widely used chemotherapeutic agent, can potentiate immune checkpoint blockade in murine tumor models...
April 2018: Science Advances
https://www.readbyqxmd.com/read/29675018/contribution-to-tumor-angiogenesis-from-innate-immune-cells-within-the-tumor-microenvironment-implications-for-immunotherapy
#6
REVIEW
Adriana Albini, Antonino Bruno, Douglas M Noonan, Lorenzo Mortara
The critical role of angiogenesis in promoting tumor growth and metastasis is strongly established. However, tumors show considerable variation in angiogenic characteristics and in their sensitivity to antiangiogenic therapy. Tumor angiogenesis involves not only cancer cells but also various tumor-associated leukocytes (TALs) and stromal cells. TALs produce chemokines, cytokines, proteases, structural proteins, and microvescicles. Vascular endothelial growth factor (VEGF) and inflammatory chemokines are not only major proangiogenic factors but are also immune modulators, which increase angiogenesis and lead to immune suppression...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29674440/lenalidomide-in-pretreated-mantle-cell-lymphoma-patients-an-italian-observational-multicenter-retrospective-study-in-daily-clinical-practice-the-lenamant-study
#7
Vittorio Stefoni, Cinzia Pellegrini, Alessandro Broccoli, Luca Baldini, Monica Tani, Emanuele Cencini, Amalia Figuera, Michela Ansuinelli, Elisa Bernocco, Maria Cantonetti, Maria Christina Cox, Filippo Ballerini, Chiara Rusconi, Carlo Visco, Luca Arcaini, Angelo Fama, Roberto Marasca, Stefano Volpetti, Alessia Castellino, Catello Califano, Marina Cavaliere, Guido Gini, Anna Marina Liberati, Gerardo Musuraca, Anna Lucania, Giuseppina Ricciuti, Lisa Argnani, Pier Luigi Zinzani
BACKGROUND: Mantle cell lymphoma (MCL) has the worst prognosis of B-cell subtypes owing to its aggressive clinical disease course and incurability with standard chemo-immunotherapy. Options for relapsed MCL are limited, although several single agents have been studied. Lenalidomide is available in Italy for patients with MCL based on a local disposition of the Italian Drug Agency. SUBJECTS, MATERIALS, AND METHODS: An observational retrospective study was conducted in 24 Italian hematology centers with the aim to improve information on effectiveness and safety of lenalidomide use in real practice...
April 19, 2018: Oncologist
https://www.readbyqxmd.com/read/29669930/tsc2-deficient-tumors-have-evidence-of-t-cell-exhaustion-and-respond-to-anti-pd-1-anti-ctla-4-immunotherapy
#8
Heng-Jia Liu, Patrick H Lizotte, Heng Du, Maria C Speranza, Hilaire C Lam, Spencer Vaughan, Nicola Alesi, Kwok-Kin Wong, Gordon J Freeman, Arlene H Sharpe, Elizabeth P Henske
Tuberous sclerosis complex (TSC) is an incurable multisystem disease characterized by mTORC1-hyperactive tumors. TSC1/2 mutations also occur in other neoplastic disorders, including lymphangioleiomyomatosis (LAM) and bladder cancer. Whether TSC-associated tumors will respond to immunotherapy is unknown. We report here that the programmed death 1 coinhibitory receptor (PD-1) is upregulated on T cells in renal angiomyolipomas (AML) and pulmonary lymphangioleiomyomatosis (LAM). In C57BL/6J mice injected with syngeneic TSC2-deficient cells, anti-PD-1 alone decreased 105K tumor growth by 67% (P < 0...
April 19, 2018: JCI Insight
https://www.readbyqxmd.com/read/29669721/ppar-%C3%AE-contributes-to-immunity-by-cancer-vaccines-that-secrete-gm-csf
#9
Girija Goyal, Karrie Wong, Christopher J Nirschl, Nicholas Souders, Donna Neuberg, Niroshana Anandasabapathy, Glenn Dranoff
Peroxisome proliferator activated receptor-γ (PPARγ) is a lipid-activated nuclear receptor that promotes immune tolerance through effects on macrophages, dendritic cells (DCs), and regulatory T cells (Tregs). Granulocyte-macrophage colony stimulating factor (GM-CSF) induces PPARγ expression in multiple myeloid cell types. GM-CSF contributes to both immune tolerance and protection, but the role of PPARγ in these pathways is poorly understood. Here we reveal an unexpected stimulatory role for PPARγ in the generation of antitumor immunity with irradiated, GM-CSF-secreting tumor-cell vaccines (GVAX)...
April 18, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29669246/tgf-%C3%AE-inhibition-and-immunotherapy-checkmate
#10
Karuna Ganesh, Joan Massagué
Immune checkpoint therapy can induce durable remissions, but many tumors demonstrate resistance. In a recent issue of Nature, Mariathasan et al. (2018) and Tauriello et al. (2018) identify stromal TGF-β signaling as a determinant of immune exclusion. Combination TGF-β inhibition and immunotherapy induces complete responses in mouse models.
April 17, 2018: Immunity
https://www.readbyqxmd.com/read/29667847/cd47-is-a-novel-potent-immunotherapy-target-in-human-malignancies-current-studies-and-future-promises
#11
Bing Tong, Mengzhao Wang
Recently, many immunosuppressive checkpoints such as PD-L1, CTLA-4 and CD47, were identified in succession and serve as potential immunotherapy targets in human cancers. Among them, CD47, a 'marker-of-self' protein that is overexpressed broadly across tumor types, is emerging as a novel potent macrophage immune checkpoint for cancer immunotherapy. In this review, we highlight the prominent role of CD47 as a 'don't-eat-me' signal that inhibits macrophage phagocytosis for immune evasion of a tumor and presents the opportunities and challenges for CD47 inhibitors both as monotherapy and in combination treatments for hematological cancers and solid tumors; some of these agents are currently in clinical trials...
April 18, 2018: Future Oncology
https://www.readbyqxmd.com/read/29667374/hepatocellular-carcinoma-prospects-for-nk-cell-immunotherapy
#12
REVIEW
N Kumar, S I Khakoo
Liver disease is a growing cause of death in the UK and the incidence of hepatocellular carcinoma (HCC) is rising (http://www.cancerresearchuk.org/). The combination of an immunosuppressive environment within the liver and suboptimal host anti-tumour immune responses may account for the poor survival outcome of HCC. Understanding how tumours evade immune recognition coupled with new insights into the unique immunological environment within the liver will be critical to developing liver-specific immunotherapies...
April 17, 2018: HLA
https://www.readbyqxmd.com/read/29667346/in-situ-vaccination-harvesting-low-hanging-fruit-on-the-cancer-immunotherapy-tree
#13
REVIEW
Mee Rie Sheen, Steven Fiering
After 100 years of debate, it is clear that cancer is recognized by the immune system and this has generated immense interest in cancer immunotherapy. The systemic nature of the immune system gives immunotherapy the ability to treat metastatic disease, which currently requires chemotherapy that frequently fails. Like chemotherapy, most immunotherapy is systemically applied in an effort to generate systemic antitumor immune response. However, local administration of immunostimulatory reagents into a recognized tumor by in situ vaccination (ISV) can also generate systemic antitumor immunity to fight metastatic disease...
April 18, 2018: Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology
https://www.readbyqxmd.com/read/29667271/syndrome-and-outcome-of-antibody-negative-limbic-encephalitis
#14
Francesc Graus, Domingo Escudero, Laura Oleaga, Jordi Bruna, Alberto Villarejo-Galende, Jordi Ballabriga, María Inés Barceló, Francisco Gilo, Stoyan Popkirov, Pavel Stourac, Josep Dalmau
OBJECTIVE: To report the clinical characteristics of 12 patients with limbic encephalitis (LE) who were antibody-negative after a comprehensive immunological study. METHODS: Review of clinical records of 163 patients with LE. Immunohistochemistry on rat brain, cultured neurons, and cell-based assays were used to identify neuronal autoantibodies. Patients were included if 1) there was adequate clinical, CSF, and MRI information to classify the syndrome as LE, 2) MRI images were accesible for central review, and 3) serum and CSF were available and confirmed negative for neuronal antibodies...
April 18, 2018: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
https://www.readbyqxmd.com/read/29667169/expression-of-scavenger-receptor-marco-defines-a-targetable-tumor-associated-macrophage-subset-in-non-small-cell-lung-cancer
#15
Linnéa La Fleur, Vanessa F Boura, Andrey Alexeyenko, Anders Berglund, Victor Pontén, Johanna Sm Mattsson, Dijana Djureinovic, Johan Persson, Hans Brunnström, Johan Isaksson, Eva Brandén, Hirsh Koyi, Patrick Micke, Mikael Ci Karlsson, Johan Botling
Tumor-associated macrophages (TAMs) are attractive targets for immunotherapy. Recently, studies in animal models showed that treatment with an anti-TAM antibody directed against the scavenger receptor MARCO resulted in suppression of tumor growth and metastatic dissemination. Here we investigated the expression of MARCO in relation to other macrophage markers and immune pathways in a non-small cell lung cancer (NSCLC) cohort (n=352). MARCO, CD68, CD163, MSR1 and programmed death ligand-1 (PD-L1) were analyzed by immunohistochemistry and immunofluorescence, and associations to other immune cells and regulatory pathways were studied in a subset of cases (n=199) with available RNA-seq data...
April 18, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29666934/quo-vadis-do-immunotherapies-have-a-role-in-glioblastoma
#16
REVIEW
Sylvia C Kurz, Patrick Y Wen
PURPOSE OF REVIEW: More effective therapies for glioblastoma are urgently needed. Immunotherapeutic strategies appear particularly promising and are therefore intensively studied. This article reviews the current understanding of the immunosuppressive glioblastoma microenvironment, discusses the rationale behind various immunotherapies, and outlines the findings of several recently published clinical studies. RECENT FINDINGS: The results of CheckMate-143 indicated that nivolumab is not superior to bevacizumab in patients with recurrent glioblastoma...
April 18, 2018: Current Treatment Options in Neurology
https://www.readbyqxmd.com/read/29666626/next-generation-immune-repertoire-sequencing-as-a-clue-to-elucidate-the-landscape-of-immune-modulation-by-host-gut-microbiome-interactions
#17
Tatsuo Ichinohe, Takahiko Miyama, Takakazu Kawase, Yasuko Honjo, Kazutaka Kitaura, Hiroyuki Sato, Tadasu Shin-I, Ryuji Suzuki
The human immune system is a fine network consisted of the innumerable numbers of functional cells that balance the immunity and tolerance against various endogenous and environmental challenges. Although advances in modern immunology have revealed a role of many unique immune cell subsets, technologies that enable us to capture the whole landscape of immune responses against specific antigens have been not available to date. Acquired immunity against various microorganisms including host microbiome is principally founded on T cell and B cell populations, each of which expresses antigen-specific receptors that define a unique clonotype...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29666300/a-pan-cancer-landscape-of-interactions-between-solid-tumors-and-infiltrating-immune-cell-populations
#18
David Tamborero, Carlota Rubio-Perez, Ferran Muiños, Radhakrishnan Sabarinathan, Josep Maria Piulats, Aura Muntasell, Rodrigo Dienstmann, Nuria Lopez-Bigas, Abel Gonzalez-Perez
PURPOSE: Throughout their development tumors are challenged by the immune system and they acquire features to evade its surveillance. A systematic view of these traits which sheds light on how tumors respond to immunotherapies is still lacking. EXPERIMENTAL DESIGN: Here, we computed the relative abundance of an array of immune cell populations to measure the immune infiltration pattern of 9,174 tumors of 29 solid cancers. We then clustered tumors with similar infiltration pattern to define immune-phenotypes...
April 17, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29666026/cervical-cancer-state-of-the-science-from-angiogenesis-blockade-to-checkpoint-inhibition
#19
REVIEW
Lindsey E Minion, Krishnansu S Tewari
Vascular endothelial growth factor (VEGF) has emerged as a therapeutic target in several malignancies, including cervical cancer. Chemotherapy doublets combined with the fully humanized monoclonal antibody, bevacizumab, now constitute first-line therapy for women struggling with recurrent/metastatic cervical carcinoma. Regulatory approval for this indication was based on the phase III randomized trial, GOG 240, which demonstrated a statistically significant and clinically meaningful improvement in overall survival when bevacizumab was added to chemotherapy: 17...
March 2018: Gynecologic Oncology
https://www.readbyqxmd.com/read/29665799/the-great-debate-at-melanoma-bridge-napoli-december-2nd-2017
#20
Paolo A Ascierto, Corrado Caracò, Jeffrey E Gershenwald, Omid Hamid, Merrick Ross, Ryan J Sullivan, Igor Puzanov
As part of the 2017 Melanoma Bridge congress (November 30-December 2, 2017, Napoli, Italy), the great debate session featured counterpoint views from leading experts on three contemporary controversial clinical issues in the care of the melanoma patient. These were: (1) whether complete lymph node dissection should be routinely offered to all melanoma patients with sentinel lymph node-positive disease; (2) whether first-line treatment of BRAF-mutated melanoma should consist of BRAF-targeted therapy or immunotherapy with checkpoint inhibitors; and (3) whether combined or sequential administration of treatments should be the preferred option in the management of patients with advanced melanoma...
April 17, 2018: Journal of Translational Medicine
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