Orchestration of Angiogenesis by Immune Cells

Abstract

It is widely accepted that the tumor microenvironment (TUMIC) plays a major role in cancer and is indispensable for tumor progression. The TUMIC involves many “players” going well beyond the malignant-transformed cells, including stromal, immune, and endothelial cells (ECs). The non-malignant cells can acquire tumor-promoting functions during carcinogenesis. In particular, these cells can “orchestrate” the “symphony” of the angiogenic switch, permitting the creation of new blood vessels that allows rapid expansion and progression toward malignancy. Considerable attention within the context of tumor angiogenesis should focus not only on the ECs, representing a fundamental unit, but also on immune cells and on the inflammatory tumor infiltrate. Immune cells infiltrating tumors typically show a tumor-induced polarization associated with attenuation of anti-tumor functions and generation of pro-tumor activities, among these angiogenesis. Here, we propose a scenario suggesting that the angiogenic switch is an immune switch arising from the pro-angiogenic polarization of immune cells. This view links immunity, inflammation, and angiogenesis to tumor progression. Here, we review the data in the literature and seek to identify the “conductors” of this “orchestra.” We also suggest that interrupting the immune → inflammation → angiogenesis → tumor progression process can delay or prevent tumor insurgence and malignant disease.

Thrombus leukocytes exhibit more endothelial cell-specific angiogenic markers than peripheral blood leukocytes do in acute coronary syndrome patients, suggesting a possibility of trans-differentiation: a comprehensive database mining study

“…It was reported that monocytes/macrophages are the most abundant inflammatory cell types of innate immunity in coronary atherothrombosis co-expressing Toll-like receptor 4 [45]. Immune cells, including Tregs, macrophages, monocytes and dendritic cells, have been shown to regulate angiogenesis in different disease settings by providing pro-angiogenic C/Cs and pro-angiogenic niches [64]. However, other roles of thrombus leukocytes, outside of the several reported roles such as triggering thrombosis, causing unstable angina and myocardial infarction, remain unknown.…”

Natural Killer Cells in the Orchestration of Chronic Inflammatory Diseases

“…Inflammation acts as a relevant orchestrator in their insurgence, development, and progression [1, 2, 6, 10]. Inflammatory cells, which comprise cells from innate ad adaptive immunity, are characterized by different phenotype and functions, which involve direct (by contact) or distant (by soluble factors) interaction with their target cells [12–14]. Immune cells, form either innate or adaptive immunity, given their cellular plasticity, have been reported to acquire an altered phenotype upon different stimuli.…”

Inhibition of vascular endothelial growth factor signaling facilitates liver repair from acute ethanol-induced injury in zebrafish

“…Immune cells can also serve as the source of VEGF signaling in organ injury (reviewed by Bruno et al, 2014). We used Tg(lyz:GFP) (Hall et al, 2007) and Tg(mpeg1:YFP) (Roca and Ramakrishnan, 2013) transgenic fish to visualize neutrophils and macrophages, respectively, after acute ethanol exposure.…”

“…Immune cells have been shown to participate in VEGF signaling in organ injury (reviewed by Bruno et al, 2014). They can directly contribute to alcoholic steatosis, angiogenesis and fibrogenesis by producing pro-inflammatory cytokines such as IL-1β and IL-6 (reviewed by Seo and Jeong, 2016).…”