The immune system plays a major role in the surveillance against tumors. To avoid attack from the immune system, tumor cells develop different strategies to escape immune surveillance. Evidence of ...immune surveillance comes from both animal models and clinical observations. Mice with a wide variety of immunodeficiencies have a high rate of tumor incidence and are more susceptible to transplanted or chemical carcinogen-induced tumors. Immunosuppressed patients have a high incidence of tumors. However, many patients develop cancer even in the presence of an apparently normal immune system. This indicates that tumor cells are able to escape immune surveillance. The aim of this review article is to summarize the literature concerning the development of the theory of immune surveillance against tumors; to discuss the evidence for and against this theory, and to discuss the concept of immunoediting. Finally, the current approaches in anti-tumor immunotherapy will be analyzed.
•THE CAM rapidly expands generating a rich vascular network.•The CAM is a pleiotropic in vivo assay.•The CAM is relatively simple, quick, and low-cost model.
During avian development the mesodermal ...layers of the allantois and chorion fuse to form the chorioallantoic membrane (CAM). This structure rapidly expands generating a rich vascular network that provides an interface for gas and waste exchange. The CAM allows to study tissue grafts, tumor growth and metastasis, drugs delivery and toxicologic analysis, and angiogenic and anti-angiogenic molecules. The CAM is relatively simple, quick, and low-cost model that allows screening of a large number of pharmacological samples in a short time; does not require administrative procedures for obtaining ethics committee approval for animal experimentation. Moreover, being naturally immunodeficient, the chick embryo may receive transplantations from different tissues and species, without immune responses.
Among the in vivo models, the chick embryo chorioallantoic membrane (CAM) has been used to implant several tumor types as well as malignant cell lines to study their growth rate, angiogenic potential ...and metastatic capability. This review article is focused on the major compelling literature data on the use of the CAM to investigate tumor growth and the metastatic process.
•The chick embryo CAM is a model for tumor biology and metastasis.•Being naturally immunodeficient, the chick embryo may receive transplantations from different tissues and species.•Compared with mammals models, tumor growth in the CAM is faster.•In contrast to standard mouse models most cancer cells complete extravasation within 24h after injections in the CAM.
Mast cells are involved in tumor growth and their mediators exert both pro- and anti-tumorigenic roles in different human cancers. The identification of defined immunosuppressive pathways that are ...present in the tumor microenvironment has pointed therapeutic strategies that may promote inflammation and/or innate immune activation in this context. Mast cells can contribute to the immune suppressive tumor microenvironment and may also enhance anti-tumor responses. This review article is focused on the analysis of the mechanisms of the role of mast cells in resistance to immunotherapy in cancer.
Endothelial cells form a single cell layer lining the inner walls of blood vessels and play critical roles in organ homeostasis and disease progression. Specifically, tumor endothelial cells are ...heterogenous, and highly permeable, because of specific interactions with the tumor tissue environment and through soluble factors and cell-cell interactions. This review article aims to analyze different aspects of endothelial cell heterogeneity in tumor vasculature, with particular emphasis on vascular normalization, vascular permeability, metabolism, endothelial-to-mesenchymal transition, resistance to therapy, and the interplay between endothelial cells and the immune system.
Endothelial cells lining the vessel wall are connected by adherent, tight and gap junctions. Adherent junctions are common to all endothelial cells, whereas tight and gap junctions graduate within ...different vascular segments. Endothelial cell-cell junctions sustain vascular homeostasis and to control the transendothelial migration of inflammatory cells. Tumor cells need to weaken endothelial cell-cell junctions to penetrate the endothelial barrier and transendothelial migration and metastasis of tumor cells are tightly controlled by endothelial cell-cell junctions.
Highlights • Mast cells and macrophages are critical regulators of inflammation and immunological response in the tumor microenvironment.. • Mast cell- and macrophages-derived growth factors are able ...to promote tumor development and angiogenesis. • Therapeutic strategies include inhibition of recruitment of mast cells and macrophages to the tumor microenvironment and blockade of pro-tumoral effects and pro-angiogenic functions.
Highlights • The name plasma cell was introduced by the anatomist von Hartz-Waldeyer in 1875. • A fully mature plasma cell lacks surface immunoglobulin expression. • Plasma cells are characterized by ...the co-expression of CD138 and CD38. • Identification of plasma cells paved the way for the development of monoclonal antibodies.
The chick embryo chorioallantoic membrane (CAM) is an extraembryonic membrane which serves as a gas exchange surface and its function is supported by a dense capillary network. Because of its ...extensive vascularization and easy accessibility, the CAM has been broadly used to study the morphofunctional aspects of the angiogenesis process in vivo and to investigate the efficacy and mechanisms of action of proangiogenic and antiangiogenic natural and synthetic molecules. The CAM has long been a favored system for the study of tumor angiogenesis and metastasis, because at this stage the chick immunocompetence system is not fully developed and the conditions for rejection have not been established. The CAM may also be used to verify the ability to inhibit the growth of capillaries by implanting tumors onto the CAM and by comparing tumor growth and vascularization with or without the administration of an antiangiogenic molecule. Other studies using the tumor cells/CAM model have focused on the invasion of the chorionic epithelium and the blood vessels by tumor cells. The cells invade the epithelium and the mesenchymal connective tissue below, where they are found in the form of a dense bed of blood vessels, which is a target for intravasation.
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