Abstract：
: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.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Hindley JP,Jones E,Smart K,Bridgeman H,Lauder SN,Ondondo B,Cutting S,Ladell K,Wynn KK,Withers D,Price DA,Ager A,Godkin AJ,Gallimore AMdoi
10.1158/0008-5472.CAN-12-1912subject
Has Abstractpub_date
2012-11-01 00:00:00pages
5473-82issue
21eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-12-1912journal_volume
72pub_type
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