Abstract 3679: VEGF-A is increased and correlates with MDSC-driven immune suppression, systemic inflammation, nutritional impairment and poor prognosis in patients with cancer

Abstract

Abstract Vascular Endothelial Growth Factor (VEGF) is a key factor for tumor progression through induction of angiogenesis and other actions including immune alteration. Myeloid-derived suppressor cells (MDSC) are a major type of immune-suppressing cell that appear in cancer or inflammation and that have been reported to express the VEGF-receptor and to be activated by VEGF. To study the clinical importance of VEGF and MDSC for cancer, peripheral blood was collected from patients with gastrointestinal, ovarian, breast, thyroid and pulmonary cancers. Peripheral blood mononuclear cells (PBMC) were separated using a Ficoll-density gradient and were used for the detection of MDSC (CD11b+CD14-CD33+) using flow cytometry and for cytokine-production assays. For these assays, PBMC were stimulated with PHA and the production of cytokines including IL-12 (Th1 inducer), IL-10, (anti-inflammatory cytokine) and IL-17, (pro-inflammatory cytokine), were measured over 24 h using ELISAs. Serum concentrations of IL-10 and VEGF were also measured using ELISAs. The serum levels of both VEGF and MDSC were significantly increased in almost all types of cancer tested and significantly correlated with each other. Their levels also significantly correlated with neutrophil/lymphocyte ratios (NLR) (inflammation marker) and CRP levels, and were inversely correlated with the PHA-stimulation index (SI) (cell mediated immune responses marker) and serum concentrations of rapid-turnover protein (RTP) (nutrition marker). VEGF levels also correlated with serum concentrations of IL-10 and VEGF, and production of IL-17, and inversely correlated with production of IL-12. The prognosis of stage IV colorectal cancer with high VEGF was significantly worse than that with low VEGF. In thyroid cancer, the number of MDSC was significantly higher, NLR and CRP levels were higher, and RTP levels were lower in patients with undifferentiated carcinoma than in those with differentiated carcinoma including papillary and follicular carcinomas. Thus VEGF was increased in cancer and correlated with immune suppression driven by MDSC, inflammation and malnutrition. Although cancer immunotherapy is currently in use for a number of cancers, MDSC have been reported to be a major inhibitor of cancer immunotherapy even in cases in which an immune checkpoint inhibitor was used. An anti-VEGF treatment strategy has now been established in combination with chemotherapy for many types of cancer. Among various types of anti-MDSC trials, anti-VEGF treatment seems to be an effective adjuvant therapy of cancer immunotherapy. Citation Format: Masahiko Shibata, Kenji Gonda, Takahiro Nakajima, Koji Kono, Hiroyuki Suzuki, Seiichi Takenoshita. VEGF-A is increased and correlates with MDSC-driven immune suppression, systemic inflammation, nutritional impairment and poor prognosis in patients with cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3679. doi:10.1158/1538-7445.AM2017-3679