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Abstract
<p class="first" id="P1">Tumor angiogenesis and escape of immunosurveillance are two
cancer hallmarks that
are tightly linked and reciprocally regulated by paracrine signaling cues of cell
constituents from both compartments. Formation and remodeling of new blood vessels
in tumors is abnormal and facilitates immune evasion. In turn, immune cells in the
tumor, specifically in context with an acidic and hypoxic environment, can promote
neovascularization. Immunotherapy has emerged as a major therapeutic modality in cancer
but is often hampered by the low influx of activated cytotoxic T-cells. On the other
hand, anti-angiogenic therapy has been shown to transiently normalize the tumor vasculature
and enhance infiltration of T lymphocytes, providing a rationale for a combination
of these two therapeutic approaches to sustain and improve therapeutic efficacy in
cancer. In this review, we discuss how the tumor vasculature facilitates an immunosuppressive
phenotype and vice versa how innate and adaptive immune cells regulate angiogenesis
during tumor progression. We further highlight recent results of antiangiogenic immunotherapies
in experimental models and the clinic to evaluate the concept that targeting both
the tumor vessels and immune cells increases the effectiveness in cancer patients.
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