Serum levels of vascular endothelial growth factor are increased and correlate with malnutrition, immunosuppression involving MDSCs and systemic inflammation in patients with cancer of the digestive system

Abstract

Vascular endothelial growth factor (VEGF) reportedly has an important role in the progression of malignant neoplasms and has been reported to induce myeloid-derived suppressor cells (MDSCs) that appear in cancer and inflammation. In the present study, serum concentrations of VEGF were measured in patients with digestive system cancer and the correlations with nutritional damage, immune suppression and systemic inflammation were analyzed. A significant increase in VEGF serum levels was observed in patients with esophageal, gastric and colorectal cancers compared with healthy volunteers. Levels of VEGF were inversely correlated with the serum concentrations of albumin, prealbumin and retinol-binding protein. The serum concentrations of VEGF were inversely correlated with the production of interleukin (IL)-12 and correlated with MDSC counts. VEGF levels were also correlated with neutrophil and neutrophil/lymphocyte counts and inversely correlated with lymphocyte count. Serum VEGF levels were divided at a cutoff of 500 pg/ml, with levels of prealbumin and retinol-binding protein significantly decreased in patients with higher VEGF levels. The stimulation index and IL-12 production were significantly decreased in the group with higher VEGF levels and MDSC counts tended to be higher in this group. These results demonstrated that increased production of VEGF was correlated with systemic inflammation, nutritional impairment and the inhibition of cell-mediated immunity involving MDSCs.

Increased neutrophil-to-lymphocyte ratio is a novel marker for nutrition, inflammation and chemotherapy outcome in patients with locally advanced and metastatic esophageal squamous cell carcinoma

“…Immune suppression was closely associated with increased NLR as the levels of SI were significantly inversely correlated to increased NLR. The authors previously reported that increasing levels of circulating myeloid-derived suppressor cells (MDSCs) correlate with decreased SI, malnutrition, and increased vascular endothelial growth factor (VEGF) levels in patients with cancer (36,37). The authors speculated that immune suppression may also occur with increased MDSC levels, activated by inflammation or tumor-produced VEGF.…”

“…The authors previously reported that malnutrition or hypoalbuminemia correlates well with immune suppression, systemic inflammation and suppression of cell-mediated immunity (34)(35)(36)(37)(38). Systemic inflammation may underlie these conditions, which are prominent in patients with advanced cancer.…”

IL-17 and VEGF are significantly associated with disease progression involving systemic inflammation in patients with gastric and colorectal cancers

“…Although a causal relationship between inflammation and the innate immunity in cancerbearing hosts is widely accepted today, the precise cellular mechanisms mediating this relationship have not been elucidated. We have reported several immunological factors, including myeloid-derived suppressor cells (MDSCs), interleukin (IL)-17, and vascular endothelial growth factor (VEGF), in various types of cancer [2][3][4] . IL-17 is a proinflammatory cytokine that is primarily secreted by T helper (Th)17 cells and innate lymphoid cells including γδT cells and natural killer cells 5,6) .…”

Endostatin improves cancer-associated systemic syndrome in a lung cancer model

“…Vascular endothelial growth factor (VEGF) is an angiogenic factor that has been characterized extensively and is expressed at high levels in the majority of tumors. In the local tumor environment, the protein modulates blood vessel growth, vascular permeability and vascular remodeling, while VEGF produced by tumors also accumulates in the circulation and induces CASS (2,8).…”

“…Cancer-associated systemic syndrome (CASS) refers to the cluster of symptoms that typically includes fever, anemia, endocrine and neurological disorders, gastrointestinal dysfunction, adipose and muscle atrophy, hepatic peliosis, ascites and kidney failure (1,2). The syndrome can also manifest as cachexia and paraneoplastic syndrome in severe cases (1,3).…”