Journal
FRONTIERS IN IMMUNOLOGY
Volume 12, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2021.811485
Keywords
immunity; immunotherapy; tumor microenvironment; endothelial cells; immune suppression; T cells; infiltration; exhaustion
Categories
Funding
- National Institutes of Health (NIH) [T32GM008076, R01NS094533, R01NS106108, R01CA241501]
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Immunotherapy shows promise in cancer treatment, but solid tumor T cell-based immunotherapy faces challenges due to lack of universal tumor-specific antigens and an immunosuppressive tumor microenvironment. The vascular microenvironment plays a crucial role in inducing immune-hostile conditions and resistance to immunotherapy in tumors.
Immunotherapy holds great promise for treating cancer. Nonetheless, T cell-based immunotherapy of solid tumors has remained challenging, largely due to the lack of universal tumor-specific antigens and an immunosuppressive tumor microenvironment (TME) that inhibits lymphocyte infiltration and activation. Aberrant vascularity characterizes malignant solid tumors, which fuels the formation of an immune-hostile microenvironment and induces tumor resistance to immunotherapy, emerging as a crucial target for adjuvant treatment in cancer immunotherapy. In this review, we discuss the molecular and cellular basis of vascular microenvironment-mediated tumor evasion of immune responses and resistance to immunotherapy, with a focus on vessel abnormality, dysfunctional adhesion, immunosuppressive niche, and microenvironmental stress in tumor vasculature. We provide an overview of opportunities and challenges related to these mechanisms. We also propose genetic programming of tumor endothelial cells as an alternative approach to recondition the vascular microenvironment and to overcome tumor resistance to immunotherapy.
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