American Association for Cancer Research
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Supplementary Figures 1-6 from T-Cell Trafficking Facilitated by High Endothelial Venules Is Required for Tumor Control after Regulatory T-Cell Depletion

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journal contribution
posted on 2023-03-30, 21:27 authored by James P. Hindley, Emma Jones, Kathryn Smart, Hayley Bridgeman, Sarah N. Lauder, Beatrice Ondondo, Scott Cutting, Kristin Ladell, Katherine K. Wynn, David Withers, David A. Price, Ann Ager, Andrew J. Godkin, Awen M. Gallimore

PDF file - 234K, S Figure 1 - Levels of Foxp3+ Tregs and T cell activation following various doses of DT treatment. S Figure 2 - Efficient depletion of Foxp3+ Tregs leads to T cell activation and proliferation. S Figure 3 - T cell accumulation in tumors of DT treated mice. S Figure 4 - Reduced tumor growth rate following depletion of Foxp3+ Tregs does not correlate with the extent of T cell activation S Figure 5 - Treg-HEV+ tumors do not contain LTi cells. S Figure 6 - Restriction of TCR repertoire in a tumor of DT treated mouse



The evolution of immune blockades in tumors limits successful antitumor immunity, but the mechanisms underlying this process are not fully understood. Depletion of regulatory T cells (Treg), a T-cell subset that dampens excessive inflammatory and autoreactive responses, can allow activation of tumor-specific T cells. However, cancer immunotherapy studies have shown 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. Cancer Res; 72(21); 5473–82. ©2012 AACR.

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