Vascular normalization as an emerging strategy to enhance cancer immunotherapy
- PMID: 23440426
- PMCID: PMC3655127
- DOI: 10.1158/0008-5472.CAN-12-4354
Vascular normalization as an emerging strategy to enhance cancer immunotherapy
Abstract
The recent approval of Provenge has brought new hope for anticancer vaccine therapies. However, the immunosuppressive tumor microenvironment seems to impair the efficacy of vaccine therapies. The abnormal tumor vasculature creates a hypoxic microenvironment that polarizes inflammatory cells toward immune suppression VSports手机版. Moreover, tumors systemically alter immune cells' proliferation, differentiation, and function via secretion of growth factors and cytokines. For example, VEGF, a major proangiogenic cytokine induced by hypoxia, plays a critical role in immunosuppression via these mechanisms. Hence, antiangiogenic treatment may be an effective modality to potentiate immunotherapy. Here, we discuss the local and systemic effects of VEGF on tumor immunity and propose a potentially translatable strategy to re-engineer the tumor-immune microenvironment and improve cancer immunotherapy by using lower "vascular normalizing" doses of antiangiogenic agents. .
©2013 AACR.
Conflict of interest statement
No potential conflicts for authors Yuhui Huang, Shom Goel, Dan G V体育安卓版. Duda and Dai Fukumura. Rakesh K. Jain received research grants from Dyax, MedImmune, and Roche; consultant fees from Dyax, Noxxon, and Zyngenia; owns equity in Enlight, SynDevRx, and XTuit; and serves on the Board of Directors of XTuit and Board of Trustees of H&Q Healthcare Investors and H&Q Life Sciences Investors. No reagents or funding from these companies were used in these studies. Therefore, there is no significant financial or other competing interest in the work.
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