Vascular normalization as an emerging strategy to enhance cancer immunotherapy

By Yuhui Huang, S. Goel, D. Duda, Dai Fukumura, Rakesh K. Jain. Cancer Research, 2013

595 citations recorded by the source corpus.

The recent approval of Provenge has brought new hope for anti-cancer 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. Moreover, tumors systemically alter immune cells’ proliferation, differentiation and function via secretion of growth factors and cytokines. For example, vascular endothelial growth factor (VEGF), a major pro-angiogenic cytokine induced by hypoxia, plays a critical role in immunosuppression via these mechanisms. Hence, anti-angiogenic 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 anti-angiogenic agents.

Subfields: Cancer Research, Immunology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/d11374c84e9c26b059c431c54a418e30989e917b

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Citations in the corpus

ANTIANGIOGENESIS STRATEGIES REVISITED: FROM STARVING TUMORS TO ALLEVIATING HYPOXIA (2014, unknown): “…and OCT4) (Lee and Simon, 2012); resistance to radiotherapy, chemotherapy, and immunotherapy (e.g., fewer oxygen radicals and cell cycle arrest) (Huang et al., 2013; Neri and Supuran, 2011; Wilson and Hay, 2011); tumor growth and genomic instability and expression of growth factors (e.g.,…”
Mechanism of action of conventional and targeted anticancer therapies: reinstating immunosurveillance. (2013, background): “These molecules ‘‘normalize’’ the tumor vasculature and revert tumor-induced alterations of the peripheral immune system, including the elevation of circulating Treg cells (Huang et al., 2013).”
The role of mechanical forces in tumor growth and therapy (2014, unknown): “Our hypothesis is that vessel compression and solid stress protect cancer cells from the immune system of the host (1, 41).”
Nanomedicine therapeutic approaches to overcome cancer drug resistance (2013, background): “Thus, the blockage of cancer specific extracellular matrix protein synthesis may lead to physiological normalization of tumor tissue structure (vascular supply) and potential reduction of resistance to conventional chemotherapy [76,77].”
Normalizing tumor microenvironment to treat cancer: bench to bedside to biomarkers. (2013, background): “trials, judicious use of vascular normalizing drugs offers new hope of improving the modest survival benefit of immunotherapies.(117) Fourth, vascular normalization can decrease intravasation of cancer cells.”