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Review
. 2013 May 15;73(10):2943-8.
doi: 10.1158/0008-5472.CAN-12-4354. Epub 2013 Feb 25.

Vascular normalization as an emerging strategy to enhance cancer immunotherapy

Affiliations
Review

Vascular normalization as an emerging strategy to enhance cancer immunotherapy

Yuhui Huang et al. Cancer Res. .

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. .

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Conflict of interest statement

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.

"V体育安卓版" Figures

Fig. 1
Fig. 1. Lower “Vascular normalizing” dose of anti-angiogenic treatment reprograms the tumor microenvironment from immunosuppressive to immunosupportive
The abnormal tumor vasculature creates a hypoxic tumor microenvironment, which impedes T effector cell infiltration into tumors and polarizes TAMs to the immune inhibitory M2-like phenotype to suppress T effector cell function. Lower dose anti-angiogenic treatment normalizes the tumor vasculature and generates a homogeneous distribution of perfused tumor vessels, facilitating the infiltration of T effector cells while reducing MDSC accumulation. In addition, improved vascular perfusion polarizes TAMs to an immune stimulatory M1-like phenotype. Thus, vascular normalization could be an effective strategy to alleviate the immunosuppressive tumor microenvironment and enhance cancer immunotherapy. Adapted from Huang et al, PNAS 2012 (8).

References

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