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The book starts with an introduction to and history of myeloid-derived suppressor cells (MDSCs), followed by a description of their differentiation, their role in the tumour microenvironment and their therapeutic targeting. It closes with an outlook on future developments. In cancer patients, myelopoiesis is perturbed and instead of generating immunogenic myeloid cells (such as dendritic cells, inflammatory macrophages and granulocytes), there is an increase in highly immature MDSCs. These cells are distributed systemically, resulting in general immunosuppression. They also infiltrate tumours, promoting their progression and metastasis by inhibiting the natural anti-tumour immune response. As these cells also interact with classical anti-neoplastic treatments, they have become major therapeutic targets in the pharmaceutical industry and in oncology research.
Analysis of multidirectional immunological responses at the tumor site allows forming a new concept of The Tumor Immunoenvironment, which is introduced and discussed in the present book with a particular focus on the role of immune cells in controlling the tumor microenvironment at different stages of cancer development. The main goal of this publication is to provide an overview of the current knowledge on the complex and unique role of the immune system, tumor-associated inflammation and tumor-mediated immunomodulation in cancer progression in a way that allows understanding the logistics of cellular and molecular interactions in the tumor lesions.
The immune system employs TLOs to elicit highly localized and forceful responses to unresolvable peripheral tissue inflammation. Current data indicate that TLOs are protective but they may also lead to collateral tissue injury and serve as nesting places to generate autoreactive lymphocytes. A better comprehension of these powerhouses of disease immunity will likely facilitate development to unprecedented and specific therapies to fight chronic inflammatory diseases.
Cells of the myeloid lineage display diverse roles and functions both in tissue homeostatic conditions and during the development of liver diseases. Hepatic myeloid cells such asKupffer cells exert immune surveillance while maintaining immune tolerance. This helps to prevent excessive immune stimulation upon encounter with gut-derived antigens from food and commensal microbes, or rapidly identifying and eliminating pathogens. Myeloid cells also exhibit a dual role by contributing to both the initiation and progression of liver diseases. During liver inflammation, myeloid cells secrete cytokines and chemokines that promote chemotaxis and tissue damage. Further down the process they can undergo reprogramming into pro-resolving, anti-inflammatory cells. In extremis, these can lead to loss of liver function and development of fibrosis and cirrhosis. Liver myeloid cells can also dictate the progress of hepatic malignancy by either promoting the infiltration and activation or suppressing the activities of effector and/or cytotoxic T cells.
The high effectiveness of antibodies as anti-tumor therapeutic agents has led to a burst of research aiming to increase their therapeutic applications by the use of antibodies against new targets, new antibody formats or new combinations. In this e-book we present relevant research depicting the current efforts in the field.
Macrophages are a key component of the innate immune system and play an integral role in host defense and homeostasis. On one hand, these cells contribute to host defence by triggering inflammation, displaying microbicidal/tumoricidal properties, regulating the activation of adaptive immunity and promoting resolution of inflammation. On the other hand, they contribute to essential trophic functions such as neural patterning, bone morphogenesis and ductal branching in mammary glands. Thus, macrophages are extremely versatile cells that can respond efficiently to tissue micro environmental cues by polarizing to distinct phenotypes, depending on the functions they need to perform. Indeed, funct...