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Laurence Zitvogel, Jonathan M Pitt, Romain Daillère, Mark J Smyth, Guido Kroemer
Fundamental cancer research and the development of efficacious antineoplastic treatments both rely on experimental systems in which the relationship between malignant cells and immune cells can be studied. Mouse models of transplantable, carcinogen-induced or genetically engineered malignancies - each with their specific advantages and difficulties - have laid the foundations of oncoimmunology. These models have guided the immunosurveillance theory that postulates that evasion from immune control is an essential feature of cancer, the concept that the long-term effects of conventional cancer treatments mostly rely on the reinstatement of anticancer immune responses and the preclinical development of immunotherapies, including currently approved immune checkpoint blockers...
September 30, 2016: Nature Reviews. Cancer
Sonia T Chelbi, Greta Guarda
The recent use of T cell-based cancer immunotherapies, such as adoptive T-cell transfer and checkpoint blockade, yields increasing clinical benefit to patients with different cancer types. However, decrease of MHC class I expression is a common mechanism transformed cells take advantage of to evade CD8(+) T cell-mediated antitumor responses, negatively impacting on the outcome of immunotherapies. Hence, there is an urgent need to develop novel approaches to overcome this limitation. NLRC5 has been recently described as a key transcriptional regulator controlling expression of MHC class I molecules...
2016: Journal for Immunotherapy of Cancer
Markus Joerger, Stephen P Finn, Sinead Cuffe, Annette T Byrne, Steven G Gray
Introduction There is strong pharmaceutical development of agents targeting the IL-17-TH17 pathway for the treatment of psoriasis (Ps) and psoriatic arthritis (PsA). Lung cancer accounts for 28% of all cancer-related deaths worldwide, and roughly 80% of patients with newly-diagnosed non-small cell lung cancer (NSCLC) present with metastatic disease, with a poor prognosis of around 12 months. Therefore, there is a high unmet medical need for the development of new and potent systemic treatments in this deadly disease...
June 29, 2016: Expert Opinion on Therapeutic Targets
A Karolina Palucka, Lisa M Coussens
Cancer heterogeneity, a hallmark enabling clonal survival and therapy resistance, is shaped by active immune responses. Antigen-specific T cells can control cancer, as revealed clinically by immunotherapeutics such as adoptive T-cell transfer and checkpoint blockade. The host immune system is thus a powerful tool that, if better harnessed, could significantly enhance the efficacy of cytotoxic therapy and improve outcomes for cancer sufferers. To realize this vision, however, a number of research frontiers must be tackled...
March 10, 2016: Cell
Florie Bertrand, Julia Rochotte, Céline Colacios, Anne Montfort, Nathalie Andrieu-Abadie, Thierry Levade, Hervé Benoist, Bruno Ségui
Tumor Necrosis Factor α (TNF) is a pleiotropic cytokine exhibiting a dual activity in oncoimmunology, either acting as a cytotoxic effector produced by leukocytes or behaving as an immunosuppressive molecule. We have just discovered that TNF signaling impairs the accumulation of tumor-infiltrating CD8(+) T lymphocytes in experimental melanoma.
2016: Oncoimmunology
Alfonso R Sanchez-Paulete, Sara Labiano, Maria E Rodriguez-Ruiz, Arantza Azpilikueta, Iñaki Etxeberria, Elixabet Bolaños, Valérie Lang, Manuel Rodriguez, M Angela Aznar, Maria Jure-Kunkel, Ignacio Melero
CD137 (4-1BB, TNF-receptor superfamily 9) is a surface glycoprotein of the TNFR family which can be induced on a variety of leukocyte subsets. On T and NK cells, CD137 is expressed following activation and, if ligated by its natural ligand (CD137L), conveys polyubiquitination-mediated signals via TNF receptor associated factor 2 that inhibit apoptosis, while enhancing proliferation and effector functions. CD137 thus behaves as a bona fide inducible costimulatory molecule. These functional properties of CD137 can be exploited in cancer immunotherapy by systemic administration of agonist monoclonal antibodies, which increase anticancer CTLs and enhance NK-cell-mediated antibody-dependent cell-mediated cytotoxicity...
March 2016: European Journal of Immunology
Sergey Vital'evich Sennikov, Julia Alexandrovna Shevchenko, Vasilii Vasil'evich Kurilin, Julia Nikolaevna Khantakova, Julia Anatol'evna Lopatnikova, Elena Vasil'evna Gavrilova, Rinat Amirovich Maksyutov, Anastasiya Yur'evna Bakulina, Sergey Vasil'evich Sidorov, Alexander Alexandrovich Khristin, Amir Zakievich Maksyutov
Advances in oncoimmunology related to the definition of the basic mechanisms of the formation of antitumor immune response, as well as the opening of tumor-associated antigens recognized by immune cells, allowed to start developing ways to influence the effector cells of the immune system to generate effective antitumor cytotoxic response. We investigated the possibility to stimulate an antitumor response in a culture of mononuclear cells of breast cancer patients by dendritic cells transfected with HLA-A*02:01-restricted DNA constructs...
February 2016: Immunologic Research
Z G Kadagidze, E G Slavina, A I Chertkova
Tumor uses various mechanisms to "escape" from immune surveillance including the important role of dysregulation of interaction of signals from corresponding co-stimulatory and co-inhibitory receptors (so-called "control points immunity"-- immune "checkpoints") modulating T-cell activation process. A creation of targeted drugs impacting on immune "checkpoints" is a new promising trend in modern oncoimmunology. This review is devoted to a brief characterization of some receptors of immune competent cells (such as activation and inhibitor), which play a crucial role in the interaction of the immune system and tumors as well as targeted drugs acting on them for therapeutic purpose...
2015: Voprosy Onkologii
A I Reppas, J C L Alfonso, H Hatzikirou
Despite recent advances in the field of Oncoimmunology, the success potential of immunomodulatory therapies against cancer remains to be elucidated. One of the reasons is the lack of understanding on the complex interplay between tumor growth dynamics and the associated immune system responses. Toward this goal, we consider a mathematical model of vascularized tumor growth and the corresponding effector cell recruitment dynamics. Bifurcation analysis allows for the exploration of model's dynamic behavior and the determination of these parameter regimes that result in immune-mediated tumor control...
2016: Virulence
N Werthmöller, B Frey, R Wunderlich, R Fietkau, U S Gaipl
One prerequisite that radiotherapy (RT) and chemotherapy (CT) result in anti-tumor immune responses is triggering of immunogenic cell death forms such as necroptosis. The latter is inducible by inhibition of apoptosis with the pan-caspase inhibitor zVAD-fmk. The design of multimodal therapies that overcome melanoma's resistance to apoptosis is a big challenge of oncoimmunology. As hints exist that immune stimulation by hyperthermia (HT) augments the efficacy of melanoma therapies and that tumors can be sensitized for RT with zVAD-fmk, we asked whether combinations of RT with dacarbazine (DTIC) and/or HT induce immunogenic melanoma cell death and how this is especially influenced by zVAD-fmk...
2015: Cell Death & Disease
Emmanouil Fokas, Eric O'Neill, Alex Gordon-Weeks, Somnath Mukherjee, W Gillies McKenna, Ruth J Muschel
Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death. Despite improvements in the clinical management, the prognosis of PDAC remains dismal. In the present comprehensive review, we will examine the knowledge of PDAC genetics and the new insights into human genome sequencing and clonal evolution. Additionally, the biology and the role of the stroma in tumour progression and response to treatment will be presented. Furthermore, we will describe the evidence on tumour chemoresistance and radioresistance and will provide an overview on the recent advances in PDAC metabolism and circulating tumour cells...
January 2015: Biochimica et Biophysica Acta
Fadi Jebbawi, Hussein Fayyad-Kazan, Makram Merimi, Philippe Lewalle, Jean-Christophe Verougstraete, Oberdan Leo, Pedro Romero, Arsene Burny, Bassam Badran, Philippe Martiat, Redouane Rouas
BACKGROUND: Recently, regulatory T (Treg) cells have gained interest in the fields of immunopathology, transplantation and oncoimmunology. Here, we investigated the microRNA expression profile of human natural CD8(+)CD25(+) Treg cells and the impact of microRNAs on molecules associated with immune regulation. METHODS: We purified human natural CD8(+) Treg cells and assessed the expression of FOXP3 and CTLA-4 by flow cytometry. We have also tested the ex vivo suppressive capacity of these cells in mixed leukocyte reactions...
2014: Journal of Translational Medicine
G B Pliss, V B Okulov, L S Potapenkova
Historical essay devoted to the life and work of Professor Tamara Alexandrovna Korosteleva (1913-1991), the former Head of the Laboratory of Oncoimmunology at the N.N. Petrov Research Institute of Oncology, St. Petersburg.
2014: Voprosy Onkologii
Erika Vacchelli, Fernando Aranda, Alexander Eggermont, Jérôme Galon, Catherine Sautès-Fridman, Laurence Zitvogel, Guido Kroemer, Lorenzo Galluzzi
In 1997, for the first time in history, a monoclonal antibody (mAb), i.e., the chimeric anti-CD20 molecule rituximab, was approved by the US Food and Drug Administration for use in cancer patients. Since then, the panel of mAbs that are approved by international regulatory agencies for the treatment of hematopoietic and solid malignancies has not stopped to expand, nowadays encompassing a stunning amount of 15 distinct molecules. This therapeutic armamentarium includes mAbs that target tumor-associated antigens, as well as molecules that interfere with tumor-stroma interactions or exert direct immunostimulatory effects...
January 1, 2014: Oncoimmunology
Jennifer Watt, Hemant M Kocher
A detailed map demonstrating the spatially restricted distribution of immune cells within the desmoplastic stroma of human pancreatic tumors opens up the field of pancreatic oncoimmunology. CD8(+) T cells located in the proximity of malignant lesions are associated with a survival advantage, suggesting the existence of immunoediting. Pancreatic stellate cells appear to dictate the infiltration of the juxtatumoral stroma by CD8(+) T cells.
December 1, 2013: Oncoimmunology
Fernando Aranda, Erika Vacchelli, Alexander Eggermont, Jerome Galon, Catherine Sautès-Fridman, Eric Tartour, Laurence Zitvogel, Guido Kroemer, Lorenzo Galluzzi
Throughout the past 3 decades, along with the recognition that the immune system not only influences oncogenesis and tumor progression, but also determines how established neoplastic lesions respond therapy, renovated enthusiasm has gathered around the possibility of using vaccines as anticancer agents. Such an enthusiasm quickly tempered when it became clear that anticancer vaccines would have to be devised as therapeutic, rather than prophylactic, measures, and that malignant cells often fail to elicit (or actively suppress) innate and adaptive immune responses...
December 1, 2013: Oncoimmunology
Vijaya B Joshi, Sean M Geary, Brett P Gross, Amaraporn Wongrakpanich, Lyse A Norian, Aliasger K Salem
Cancer vaccines that use tumor lysate (TL) as a source of tumor-associated antigens (TAAs) have significant potential for generating therapeutic anti-tumor immune responses. Vaccines encompassing TL bypass the limitations of single antigen vaccines by simultaneously stimulating immunity against multiple TAAs, thereby broadening the repertoire of TAA-specific T-cell clones available for activation. Administration of TL in particulate form, such as when encapsulated in biodegradable microparticles, increases its immunostimulatory capacity and produces more robust immune responses than when TL is given in soluble form...
January 2014: Expert Review of Vaccines
Dmitriy W Gutkin, Michael R Shurin
The immune system has a dual role in cancer development and progression. On the one hand, it can eradicate emerging malignant cells, but on the other hand, it can actively promote growth of malignant cells, their invasive capacities and their ability to metastasize. Immune cells with predominantly anti-tumor functionality include cells of the innate immune system, such as natural killer cells, and cells of adaptive immunity, such as conventional dendritic cells and cytotoxic T lymphocytes. Immune cells with predominantly pro-tumor functionality include a broad spectrum of cells of the innate and adaptive immune system, such as type 2 neutrophils and macrophages, plasmacytoid DC, myeloid-derived suppressor cells and regulatory T lymphocytes...
January 2014: Cancer Immunology, Immunotherapy: CII
Erika Vacchelli, Alexander Eggermont, Catherine Sautès-Fridman, Jérôme Galon, Laurence Zitvogel, Guido Kroemer, Lorenzo Galluzzi
Toll-like receptors (TLRs) have long been known for their ability to initiate innate immune responses upon exposure to conserved microbial components such as lipopolysaccharide (LPS) and double-stranded RNA. More recently, this family of pattern recognition receptors has been attributed a critical role in the elicitation of anticancer immune responses, raising interest in the development of immunochemotherapeutic regimens based on natural or synthetic TLR agonists. In spite of such an intense wave of preclinical and clinical investigation, only three TLR agonists are currently licensed by FDA for use in cancer patients: bacillus Calmette-Guérin (BCG), an attenuated strain of Mycobacterium bovis that operates as a mixed TLR2/TLR4 agonist; monophosphoryl lipid A (MPL), a derivative of Salmonella minnesota that functions as a potent agonist of TLR4; and imiquimod, a synthetic imidazoquinoline that activates TLR7...
August 1, 2013: Oncoimmunology
Erika Vacchelli, Alexander Eggermont, Wolf Hervé Fridman, Jérôme Galon, Laurence Zitvogel, Guido Kroemer, Lorenzo Galluzzi
During the past two decades, the notion that cancer would merely constitute a cell-intrinsic disease has gradually been complemented by a model postulating that the immune system plays a relevant role during all stages of oncogenesis and tumor progression. Along with this conceptual shift, several strategies have been devised to stimulate tumor-specific immune responses, including relatively unselective approaches such as the systemic administration of adjuvants or immunomodulatory cytokines. One year ago, in the July issue of OncoImmunology, we described the main biological features of this large group of proteins and discussed the progress of ongoing clinical studies evaluating their safety and therapeutic potential in cancer patients...
July 1, 2013: Oncoimmunology
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