Immunomodulation of Tumor Vessels: It Takes Two to Tango. Issue 10 (October 2018)

• Record Type: Journal Article
• Authors: Johansson-Percival, Anna; He, Bo; Ganss, Ruth
• Is Part Of: Trends in immunology. Volume 39:Issue 10(2018)
• Page Start: 801
• Page End: 814
• Publication Date: 2018-10
• Subjects: Immunology -- Periodicals; 571.96
• DOI: 10.1016/j.it.2018.08.001
• Languages: English
• ISSNs: 1471-4906

Abstract

Abstract : The density of intratumoral CD8 + T cells predicts patient survival and responsiveness to immunotherapy. Effector T cell infiltration in turn is controlled by the tumor vasculature which co-evolves together with an immune-suppressive environment. At the T cell–vascular interface, endothelial cells actively suppress T cell trafficking and function. Conversely, forced activation, normalization, and differentiation of tumor vessels into high endothelial venule entrance portals for lymphocytes can facilitate T cell extravasation. Emerging evidence demonstrates that this process is not exclusively controlled by the endothelium. Indeed, tumor vasculature and CD4 + and/or CD8 + T cells may regulate each other: increasing local effector T cell numbers or re-invigorating pre-existing T cells via immune checkpoint blockade can directly affect the vasculature. A deeper understanding of the orchestration and duration of this reciprocal relationship may help shape the design of future immunotherapies. Highlights: Effector CD4 + and CD8 + T cells are key drivers of combined antiangiogenesis and checkpoint blockade immunotherapies in solid cancers. Reciprocal interactions between the tumor endothelium and effector CD8 + T cells can regulate T cell migration across the tumor vascular barrier. Mutual and self-amplifying regulation of tumor vessel normalization can be mediated by effector T cells. Effector CD8 + T cells are key players in IFNγ-mediated vessel regression. Effector CD4 + and CD8 + T cells can mediate therapeutic induction of high endothelial venules in certain solid cancers.