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The activation of adaptive immune responses requires the processing and presentation of protein antigens to lymphocytes. Especially dendritic cells are effective at display of antigen-derived peptides in the form of immunogenic peptide/MHC complexes to CD4 and CD8-positive T cells, and can stimulate even naive T cells to clonally expand. During the last 40 years, mechanisms that facilitate antigen processing and presentation were clarified, mostly from work in cell lines and mouse models. From mouse-based work, it is now clear that dendritic cells represent a collection of specialized cell subsets that are particularly well endowed to stimulate antigen transport to distinct tissue locations, to transfer antigens between cellular subsets or to trigger T cell responses. Dendritic cell subsets hold great promise for therapeutic application, for example as dendritic cell-based vaccines to bolster immune responses against viruses or malignant growths. Hurdles remain that preclude the efficient application of high quality pre-clinical research into standardized patient care. In this research topic, efforts in dendritic cell research and dendritic cell-based vaccines are discussed, from both pre-clinical and application points of view.

clinical translation --- cross-presentation --- Vaccination --- Immunotherapy --- dendritic cell

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The activation of adaptive immune responses requires the processing and presentation of protein antigens to lymphocytes. Especially dendritic cells are effective at display of antigen-derived peptides in the form of immunogenic peptide/MHC complexes to CD4 and CD8-positive T cells, and can stimulate even naive T cells to clonally expand. During the last 40 years, mechanisms that facilitate antigen processing and presentation were clarified, mostly from work in cell lines and mouse models. From mouse-based work, it is now clear that dendritic cells represent a collection of specialized cell subsets that are particularly well endowed to stimulate antigen transport to distinct tissue locations, to transfer antigens between cellular subsets or to trigger T cell responses. Dendritic cell subsets hold great promise for therapeutic application, for example as dendritic cell-based vaccines to bolster immune responses against viruses or malignant growths. Hurdles remain that preclude the efficient application of high quality pre-clinical research into standardized patient care. In this research topic, efforts in dendritic cell research and dendritic cell-based vaccines are discussed, from both pre-clinical and application points of view.

clinical translation --- cross-presentation --- Vaccination --- Immunotherapy --- dendritic cell

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Significant efforts over the last two decades have been made to better understand the factors that control DC maturation and activation and the impact of these processes on overall host immunity. In addition to the well-characterized role of DC in the induction of immunity to pathogens, a role for these cells as critical regulators of anti-tumor immune responses has more recently become apparent. These findings have generated interest in understanding how tumor/DC interactions impact the quality of anti-tumor immune responses, and they have contributed to increased enthusiasm for a variety of DC-based cancer immunotherapies. Such strategies have included DNA- or peptide-based vaccines that involve uptake and processing of tumor antigens by endogenous DC in cancer patients or the administration of tumor antigen-loaded exogenous DC-based vaccines. Additionally, many adjuvant, cytokine, and monoclonal antibody therapies aim either to enhance the immunostimulatory capacity of endogenous DC or to supplement the activity of these cells by targeting costimulatory receptors on T cells. Despite the promise of such therapeutic approaches for cancer treatment, their success is often limited, and much remains to be understood about how tumors influence DC function and the quality of DC-mediated immune responses. Tumor/DC interactions have therefore become an increasingly active area of investigation, and many studies have described effects of tumors on DC phenotype and function that include an accumulation of immature DC within tumors, tumor-altered differentiation of DC precursors into myeloid-derived suppressor cells, and the generation of tumor-associated DC with immunoregulatory properties. As this field moves forward, it will be important to gain mechanistic insights into the basis for both tumor-mediated DC dysfunction as well as the induction of either suboptimal or immunosuppressive adaptive anti-tumor immune responses by tumor-associated DC. Progress in these areas of tumor immunology will greatly improve our understanding of the factors that contribute to effective DC-mediated anti-tumor immune control versus DC-associated anti-tumor immune dysfunction and subsequent tumor immune escape. Such information is vital for improving current and developing novel immunotherapeutic strategies for interfering with tumor-associated DC dysfunction and enhancing the functional quality of endogenous DC in cancer patients as well as the efficacy of exogenous DC-based anti-tumor vaccines. The articles contained within this special issue highlight these important topics and bring focus not only to our current understanding of tumor/DC interactions but also to major areas of investigation that remain ongoing in this field.

Dendritic cells. --- Tumors. --- cross-presentation --- tumor --- cancer immunotherapy --- Immune Regulation --- dendritic cell --- tumor immune evasion

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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

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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