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Arginase is an enzyme that is involved in many pathologies such as cardiovascular diseases (artherolscleroses, diabetes, hypertension, etc.), asthma and cancers. They were the ones who interested us. Indeed, the isoenzyme 1 of arginase is produced in large quantities by the MDSCs and TAMs which are immune cells that have been recruited by the cancer cells. Their arginase production causes L-arginine depletion, ROS production and increased L-ornithine concentrations; which leads to the promotion of tumor growth and its escape to the immune system. The development of an inhibitor of this enzyme therefore seems to be an interesting way of counteracting its pro-tumor effects. This led to the discovery of ABH, which is an alpha-amino acid whose side chain is substituted with a boric acid. Hence modulations have been carried out to discover the tropanic derivatives which are the molecules present at the present time the best inhibitory properties of the enzyme and a relative selectivity for arginase 1 compared to arginase 2. However, the bioavailability of these was poor. But it can be assumed that this disadvantage would have been resolved by the pharmaceutical company Calithera Bioscineces, since they announced the discovery of CB-1158 as the first selective inhibitor of arginase possessing and IC50 of the order of nM and being and is currently in Phase 1 clinical trials. L’arginase est une enzyme qui est impliquée dans de nombreuses pathologies telles que les maladies cardio-vasculaires (athérosclérose, diabète, hypertension, etc.), l’asthme, ou encore les cancers. Ce sont ces derniers qui nous ont intéressés. En effet, l’isoenzyme 1 de l’arginase y est produite en grande quantité par les MDSCs et les TAMs qui sont des cellules immunitaires qui ont été recrutées par les cellules cancéreuses. Leur production d’arginase cause une déplétion en L-arginine, une production de ROS et une augmentation des concentrations en L-ornithine ; ce qui conduit à la favorisation de la croissance tumorale et à son échappement au système immunitaire. Le développement d’inhibiteur de cette enzyme semble donc être une voie intéressante pour contrer ses effets pro-tumoraux. Celui-ci a mené à la découverte de l’ABH, qui est un acide alpha-aminé dont la chaîne latérale est substituée par un acide borique. De l) des modulations ont été réalisées pour aboutir à la découverte des dérivés tropaniques qui sont les molécules présentant à l’heure actuelle les meilleures propriétés inhibitrices de l’enzyme et une relative sélectivité pour l’arginase 1 par rapport à l’arginase 2. Cependant, la biodisponibilité de ceux-ci laissait à désirer. Mais on peut supposer que cet inconvénient aurait été résolu par la société pharmaceutique Calithera Biosciences, vu qu’ils ont annoncé la découverte du CB-1158 comme étant le premier inhibiteur sélectif de l’arginase possédant un IC50 de l’ordre du nM et étant actif par voie orale et que celui-ci est actuellement en tests cliniques de phase 1.

Arginase --- Myeloid-Derived Suppressor Cells --- Macrophages --- Neoplasms

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Haptens. --- Immunological tolerance. --- Immunosuppression. --- Autoantibodies --- Haptens --- Immunity, Cellular. --- Hapten. --- Molekül. --- immunology. --- AUTOIMMUNITY --- DERMATITIS, CONTACT --- HAPTENS --- IGG --- IMMUNE TOLERANCE --- MAJOR HISTOCOMPATIBILITY COMPLEX --- SUPPRESSOR CELLS --- T-LYMPHOCYTES --- IMMUNOLOGY

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In this book, we present a compilation of original research articles as well as review articles that are focused on improving our understanding of the molecular and cellular mechanisms by which cancer cells adapt to their microenvironment. These include the interplay between cancer cells and the surrounding microenvironmental cells (e.g., macrophages, tumor-infiltrating lymphocytes and myeloid cells) and microenvironmental environments (e.g., oxidative stress, pH, hypoxia) and the implications of this dynamic interaction to tumor radioresistance, chemoresistance, invasion and metastasis. Finally, the importance and relevance of these findings are translated to cancer therapy.

Medicine --- hypoxia --- macrophages --- colon cancer --- tumor microenvironment --- immune cell infiltration --- prognosis --- feline mammary carcinoma --- PD-1 --- PD-L1 --- CTLA-4 --- TNF-α --- biomarkers --- immunotherapy --- cancer --- histone modification --- inhibitor --- KDM5B --- molecular docking --- repurposing --- cancer acidity --- hyperosmolarity --- cross-presentation --- tumour microenvironment --- syngeneic model --- prostate cancer --- radiotherapy --- preclinical modelling --- myeloid-derived suppressor cells --- biomarker --- stroma --- cancer-associated fibroblast (CAF) --- extracellular matrix (ECM) --- cytokine/chemokine --- growth factors --- pro- and anti-tumor immune cells --- immunomodulatory roles --- radiotherapy dose fractionation --- radioresistance --- radiosensitivity --- breast cancer --- S100A10 (p11) --- tumor growth --- tumor progression --- metastasis --- carcinoma --- mammary gland --- triple negative --- pre-metastatic niche --- pro-inflammatory cytokines --- clinical trials --- evolutionary therapy --- darwinian evolution --- cancer cells subpopulations --- diclofenac --- koningic acid --- spheroid --- 3D co-culture --- microenvironment --- resistance --- myeloid cells --- cancer development --- molecular subtypes of pancreatic cancer --- chemotherapy response --- pancreatic stellate cells --- regulatory T cells --- tumor-associated macrophages --- myeloid derived suppressor cells --- glioblastoma (GB) --- Hypoxia Inducible Factor (HIF) --- glioma stem cells (GSC) --- oxidative stress --- reactive oxygen species --- plasmin --- plasminogen --- S100A10 --- uPA --- uPAR --- PAI-1 --- PAI-2 --- cancer stem cells --- cancer recurrence --- therapeutic resistance --- signaling pathways --- targeted therapy --- head and neck cancer --- lung cancer --- bladder cancer --- hypoxia --- macrophages --- colon cancer --- tumor microenvironment --- immune cell infiltration --- prognosis --- feline mammary carcinoma --- PD-1 --- PD-L1 --- CTLA-4 --- TNF-α --- biomarkers --- immunotherapy --- cancer --- histone modification --- inhibitor --- KDM5B --- molecular docking --- repurposing --- cancer acidity --- hyperosmolarity --- cross-presentation --- tumour microenvironment --- syngeneic model --- prostate cancer --- radiotherapy --- preclinical modelling --- myeloid-derived suppressor cells --- biomarker --- stroma --- cancer-associated fibroblast (CAF) --- extracellular matrix (ECM) --- cytokine/chemokine --- growth factors --- pro- and anti-tumor immune cells --- immunomodulatory roles --- radiotherapy dose fractionation --- radioresistance --- radiosensitivity --- breast cancer --- S100A10 (p11) --- tumor growth --- tumor progression --- metastasis --- carcinoma --- mammary gland --- triple negative --- pre-metastatic niche --- pro-inflammatory cytokines --- clinical trials --- evolutionary therapy --- darwinian evolution --- cancer cells subpopulations --- diclofenac --- koningic acid --- spheroid --- 3D co-culture --- microenvironment --- resistance --- myeloid cells --- cancer development --- molecular subtypes of pancreatic cancer --- chemotherapy response --- pancreatic stellate cells --- regulatory T cells --- tumor-associated macrophages --- myeloid derived suppressor cells --- glioblastoma (GB) --- Hypoxia Inducible Factor (HIF) --- glioma stem cells (GSC) --- oxidative stress --- reactive oxygen species --- plasmin --- plasminogen --- S100A10 --- uPA --- uPAR --- PAI-1 --- PAI-2 --- cancer stem cells --- cancer recurrence --- therapeutic resistance --- signaling pathways --- targeted therapy --- head and neck cancer --- lung cancer --- bladder cancer

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In this book, we present a compilation of original research articles as well as review articles that are focused on improving our understanding of the molecular and cellular mechanisms by which cancer cells adapt to their microenvironment. These include the interplay between cancer cells and the surrounding microenvironmental cells (e.g., macrophages, tumor-infiltrating lymphocytes and myeloid cells) and microenvironmental environments (e.g., oxidative stress, pH, hypoxia) and the implications of this dynamic interaction to tumor radioresistance, chemoresistance, invasion and metastasis. Finally, the importance and relevance of these findings are translated to cancer therapy.

hypoxia --- macrophages --- colon cancer --- tumor microenvironment --- immune cell infiltration --- prognosis --- feline mammary carcinoma --- PD-1 --- PD-L1 --- CTLA-4 --- TNF-α --- biomarkers --- immunotherapy --- cancer --- histone modification --- inhibitor --- KDM5B --- molecular docking --- repurposing --- cancer acidity --- hyperosmolarity --- cross-presentation --- tumour microenvironment --- syngeneic model --- prostate cancer --- radiotherapy --- preclinical modelling --- myeloid-derived suppressor cells --- biomarker --- stroma --- cancer-associated fibroblast (CAF) --- extracellular matrix (ECM) --- cytokine/chemokine --- growth factors --- pro- and anti-tumor immune cells --- immunomodulatory roles --- radiotherapy dose fractionation --- radioresistance --- radiosensitivity --- breast cancer --- S100A10 (p11) --- tumor growth --- tumor progression --- metastasis --- carcinoma --- mammary gland --- triple negative --- pre-metastatic niche --- pro-inflammatory cytokines --- clinical trials --- evolutionary therapy --- darwinian evolution --- cancer cells subpopulations --- diclofenac --- koningic acid --- spheroid --- 3D co-culture --- microenvironment --- resistance --- myeloid cells --- cancer development --- molecular subtypes of pancreatic cancer --- chemotherapy response --- pancreatic stellate cells --- regulatory T cells --- tumor-associated macrophages --- myeloid derived suppressor cells --- glioblastoma (GB) --- Hypoxia Inducible Factor (HIF) --- glioma stem cells (GSC) --- oxidative stress --- reactive oxygen species --- plasmin --- plasminogen --- S100A10 --- uPA --- uPAR --- PAI-1 --- PAI-2 --- cancer stem cells --- cancer recurrence --- therapeutic resistance --- signaling pathways --- targeted therapy --- head and neck cancer --- lung cancer --- bladder cancer

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DNA is a rapidly developing vaccine platform for cancer and infectious and non-infectious diseases. Plasmids are used as immunogens to encode proteins to be further synthesized in vaccine recipients. DNA is mainly synthetic, ensuring enhanced expression in the cells of vaccine recipients (mostly mammalians). Their introduction into the host induces antibody and cellular responses. The latter are often more pronounced, and mimic the events occurring in infection, especially viral. There are a few distinct ways in which the vaccine antigen can be processed and presented, which determine the resulting immune response and which can be manipulated. Routinely, the antigen synthesized within the host cell is processed by proteasome, loaded onto, and presented in a complex with MHC I molecules. Processing can be re-routed to the lysosome, or immunogen can be secreted for further presentation in a complex with MHC II. Apart from expression, vaccination efficacy depends on DNA delivery. DNA immunogens are generally administered by intramuscular or intradermal injections, usually followed by electroporation, which enhances delivery 1000-fold. Other techniques are also used, such as noninvasive introduction by biojectors, skin applications with plasters and microneedles/chips, sonication, magnetofection, and even tattooing. An intense debate regarding the pros and cons of different routes of delivery is ongoing. A number of studies have compared the effect of delivery methods at the level of immunogen expression, and the magnitude and specificity of the resulting immune response. According to some, the delivery route determines immunogenic performance; according to others, it can modulate the level of response, but not its specificity or polarity. The progress of research aiming at the optimization of DNA vaccine design, delivery, and immunogenic performance has led to a marked increase in their efficacy in large species and humans. New DNA vaccines for use in the treatment of infectious diseases, cancer, allergies, and autoimmunity are forthcoming. This Special Issue covers various aspects of DNA vaccine development.

Medicine --- Epidemiology & medical statistics --- alphaviruses --- layered RNA/DNA vectors --- DNA vaccines --- RNA replicons --- recombinant particles --- tumor regression --- protection against tumor challenges and infectious agents --- ebola virus disease --- artificial T-cell antigens --- DNA vaccine constructs --- computer design --- gene expression --- immunogenicity --- DNA vaccine --- mRNA vaccine --- plasmid DNA --- in vitro transcribed mRNA --- immune responses --- formulations --- Cytolytic T Lymphocytes --- antibodies --- innate immunity --- adjuvants --- vaccine delivery --- plasmid --- cytolytic --- perforin --- bicistronic --- HCV --- HIV --- IL-36 --- adjuvant --- DNA --- Zika --- Epstein-Barr virus --- latent proteins --- LMP2 --- EBNA1 --- LMP1 --- HIV-1 --- enhancer element --- circovirus --- influenza --- immunization --- intranasal --- lipid --- flagellin --- BCG --- vaccine --- rBCG --- HTI --- T-cell --- AIDS --- clinical trial --- therapeutic vaccine --- hepatitis C virus (HCV) --- mesenchymal stem cells (MSC) --- modified MSC --- DNA immunization --- nonstructural HCV proteins --- immune response --- HCV vaccine --- myeloid derived suppressor cells (MDSCs) --- n/a