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  • Opinion
  • Published:

Improving immune–vascular crosstalk for cancer immunotherapy

Abstract

The vasculature of tumours is highly abnormal and dysfunctional. Consequently, immune effector cells have an impaired ability to penetrate solid tumours and often exhibit compromised functions. Normalization of the tumour vasculature can enhance tissue perfusion and improve immune effector cell infiltration, leading to immunotherapy potentiation. However, recent studies have demonstrated that the stimulation of immune cell functions can also help to normalize tumour vessels. In this Opinion article, we propose that the reciprocal regulation between tumour vascular normalization and immune reprogramming forms a reinforcing loop that reconditions the tumour immune microenvironment to induce durable antitumour immunity. A deeper understanding of these pathways could pave the way for identifying new biomarkers and developing more effective combination treatment strategies for patients with cancer.

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Figure 1: Abnormalities in the tumour vasculature contribute to immune suppression via multiple mechanisms.
Figure 2: A reinforcing feedback loop of immune reprogramming and tumour vascular normalization.
Figure 3: Biomarker discovery for immuno-oncology.

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Acknowledgements

This work was supported by grants from the National Program on Key Research Project of China (2016YFC1302404; Y.H.), the National Natural Science Foundation of China (81673004, 81372245; Y.H.), the fund of the Distinguished Professors of Jiangsu Province (SR21100114), the Collaborative Innovation Center of Hematology, the Priority Academic Program Development of Jiangsu Higher Education Institutions, the Mayo Clinic Center for Regenerative Medicine (B.Y.S.K.), the Jorge and Leslie Bacardi fund for the study of Regenerative Medicine (B.Y.S.K.), the National Institute of Neurological Disorders and Stroke Grant R01 NS104315 (B.Y.S.K.), the American Society of Clinical Oncology (ASCO) Conquer Cancer Foundation Young Investigator Award (W.J.) and the National Cancer Institute's Cancer Center Support (Core) Grant CA016672 (to The University of Texas MD Anderson Cancer Center). The authors thank C. Wogan of MD Anderson Cancer Center's Division of Radiation Oncology for editorial assistance.

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Y.H. and W.J. conceived the study. Y.H. and W.J. performed the literature search. Y.H., B.Y.S.K. and W.J. designed and generated the figures. All authors helped to write the manuscript.

Corresponding authors

Correspondence to Yuhui Huang, Betty Y. S. Kim or Wen Jiang.

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Huang, Y., Kim, B., Chan, C. et al. Improving immune–vascular crosstalk for cancer immunotherapy. Nat Rev Immunol 18, 195–203 (2018). https://doi.org/10.1038/nri.2017.145

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