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T-cell trafficking facilitated by high endothelial venules is required for tumor control after regulatory T cell depletion

Hindley, James Phillip, Jones, Emma, Smart, Kathryn, Bridgeman, Hayley, Lauder, Sarah Nicol, Ondondo, Beatrice Omusiro, Cutting, Scott, Ladell, Kristin Ingrid, Wynn, Katherine Kay, Withers, David, Price, David, Ager, Ann, Godkin, Andrew James and Gallimore, Awen Myfanwy 2012. T-cell trafficking facilitated by high endothelial venules is required for tumor control after regulatory T cell depletion. Cancer Research 72 (21) , pp. 5473-5482. 10.1158/0008-5472.CAN-12-1912

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Abstract

The evolution of immune blockades in tumors limits successful anti-tumor immunity, but the mechanisms underlying this process are not fully understood. Depletion of regulatory T cells (Tregs), a T cell subset that dampens excessive inflammatory and autoreactive responses, can allow activation of tumor-specific T cells. However, cancer immunotherapy studies have demonstrated that a persistent failure of activated lymphocytes to infiltrate tumors remains a fundamental problem. In evaluating this issue, we found that despite an increase in T cell activation and proliferation following Treg depletion there was no significant association with tumor growth rate. In contrast, there was a highly significant association between low tumor growth rate and the extent of T cell infiltration. Further analyses revealed a total concordance between low tumor growth rate, high T cell infiltration and the presence of high endothelial venules (HEV). HEV are blood vessels normally found in secondary lymphoid tissue where they are specialized for lymphocyte recruitment. Thus, our findings suggest that Treg depletion may promote HEV neogenesis, facilitating increased lymphocyte infiltration and destruction of the tumor tissue. These findings are important as they point to a hitherto unidentified role of Tregs, the manipulation of which may refine strategies for more effective cancer immunotherapy.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Publisher: American Association for Cancer Research
ISSN: 0008-5472
Last Modified: 11 Sep 2018 21:19
URI: http://orca.cf.ac.uk/id/eprint/37461

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