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Editorial
. 2017 Dec;5(24):497.
doi: 10.21037/atm.2017.10.12.

Antiangiogenic therapy and immune checkpoint blockade go hand in hand

Luis Felipe Campesato  1 , Taha Merghoub  1
Affiliations
Editorial

Antiangiogenic therapy and immune checkpoint blockade go hand in hand

Luis Felipe Campesato et al. Ann Transl Med. 2017 Dec.
No abstract available

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Conflict of interest statement

Conflicts of Interest: The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Illustration of proposed mechanism for combination therapy with anti-vascular endothelial growth factor (VEGF)/VEGFR2 and immune checkpoint blockade (ICB). On the left: tumor with abnormal vessels, characterized by a defective structure, poor pericyte coverage, areas of hypoxia and impaired T cell infiltration. On the right: tumor after antiangiogenic therapy with a normalized vasculature; enhanced pericyte coverage, expression of adhesion molecules and increased T cell infiltration. The formation of HEVs leads to more efficient T cell influx into tumors. IFNy-mediated expression of immune inhibitory checkpoint molecules, such as PD-L1, can be counteracted by the use of ICB promoting more efficient tumor control.
Figure 2
Figure 2
Proposed scheme for rational combinatorial therapy strategies based on characteristic of the tumor microenvironment. (A) Tumor with a pre-existing immunity, which are defined by high T cell infiltration, a gene signature associated with interferon (IFN) signaling and high expression of PD-L1, are exemplified in an immunohistochemistry (IHC) staining of CD8 (brown) in a tumor section. Tumors presenting these features are associated with good response to Immune checkpoint blockade (ICB) interventions alone. (B) Tumors lacking T cell infiltration (as exemplified in the IHC staining of CD8) and other inflammatory features, such as IFN-signature and PD-L1 expression, are generally not good responders to ICB therapy alone. Combinatorial strategies using antiangiogenic drugs, which promote normalization of the blood vessel structure and potentially more efficient immune cell trafficking into the tumor tissue, can work on sensitizing immune “cold” tumors to the use of ICB therapy.
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References

    1. Khalil DN, Smith EL, Brentjens RJ, et al. The future of cancer treatment: immunomodulation, CARs and combination immunotherapy. Nat Rev Clin Oncol 2016;13:394. 10.1038/nrclinonc.2016.65 - DOI - PMC - PubMed
    1. Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases. Nature 2000;407:249-57. 10.1038/35025220 - DOI - PubMed
    1. Motz GT, Coukos G. The parallel lives of angiogenesis and immunosuppression: cancer and other tales. Nat Rev Immunol 2011;11:702-11. 10.1038/nri3064 - DOI - PubMed
    1. Nagy JA, Chang S-H, Dvorak AM, et al. Why are tumour blood vessels abnormal and why is it important to know? Br J Cancer 2009;100:865-9. 10.1038/sj.bjc.6604929 - DOI - PMC - PubMed
    1. Jayson GC, Kerbel R, Ellis LM, et al. Antiangiogenic therapy in oncology: current status and future directions. Lancet 2016;388:518-29. 10.1016/S0140-6736(15)01088-0 - DOI - PubMed

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