Angiogenesis and Lymphangiogenesis in Gastrointestinal Tumor Microenvironment: From Molecular to Clinical Aspects

Dear Colleagues,

Cancer development is a multistep process characterized by genetic and epigenetic alterations during tumor initiation and progression. The stromal microenvironment is important in maintaining normal tissue homeostasis or promoting tumor development. A plethora of immune cells (i.e., lymphocytes, macrophages, mast cells, monocytes, myeloid-derived suppressor cells, dendritic cells, neutrophils, eosinophils, natural killer (NK) and natural killer T (NKT) cells are components of cancer microenvironment. In the organs and tissues in contact with the external environment as skin and gastrointestinal system, the role of immune stromal cells is to defend the organism from pathogenic insults including cancers cells. Immune stromal cells density is increased in cancer and there is a correlation with angiogenesis, the number of metastatic lymph nodes and the survival of these patients. These cells exert a pro-tumorigenic role in cancer through the release of classical and non classical angiogenic (VEGF-A, CXCL-8, MMP-9, Tryptase, Chymase) and lymphangiogenic factors (VEGF-C, VEGF-F and PDPN). These cells express also the programmed death ligands (PD-L1 and PD-L2) which are relevant as immune checkpoints in cancer. Several clinical undergoing trials targeting immune checkpoints could be an innovative therapeutic strategy in cancer. Elucidation of the role of subsets of cells in different human cancers will demand studies of increasing complexity beyond those assessing merely cell density and micro-localization. The aim of this special issue is to evaluate from molecular biology to immunohistochemical analysis, specific immune stromal cells in tumor microenvironment, correlating these cells and their release factors with neo-angiogenesis and lymphangiogenesis, and investigating their role as possible novel biomarkers and new therapeutic strategies.

Dr. Michele Ammendola
Guest Editor

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