Increasing evidence supports the existence of elevated numbers of regulatory T cells (T-reg cells) in solid tumors and hematologic malignancies. Whereas the biology of CD4(+)CD25(+)FOXP3(+) T,9 cells in murine models seems to be rather straightforward, studies in human diseases are more difficult to interpret due to expression of CD25 on activated effector T cells as well as Treg cells. More importantly, early studies in human tumors were mainly focused on CD4(+)CD25(+) T-reg cells lacking interrogation of more specific markers such as FOXP3 expression. Although the increase of T-reg cells seems to be a characteristic feature in most tumors, little is known about the molecular and cellular mechanisms responsible for the increase and maintenance of elevated levels of T-reg cells in cancer. We will discuss earlier data in the context of recent findings in Treg-cell biology with a particular emphasis on CD4(+)CD25(high)FOXP3(+) T-reg cells in human malignancies.
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