FOXP3 Expression Accurately Defines the Population of Intratumoral Regulatory T Cells That Selectively Accumulate in Metastatic Melanoma Lesions

Overview

Journal Blood

Publisher Elsevier

Specialty Hematology

Date 2008 Sep 30

PMID 18820132

Citations 71

Authors

Mojgan Ahmadzadeh

Aloisio Felipe-Silva

Bianca Heemskerk

Daniel J Powell Jr

John R Wunderlich

Maria J Merino

Steven A Rosenberg

Affiliations

Soon will be listed here.

Abstract

Regulatory T (T(reg)) cells are often found in human tumors; however, their functional characteristics have been difficult to evaluate due to low cell numbers and the inability to adequately distinguish between activated and T(reg) cell populations. Using a novel approach, we examined the intracellular cytokine production capacity of tumor-infiltrating T cells in the single-cell suspensions of enzymatically digested tumors to differentiate T(reg) cells from effector T cells. Similar to T(reg) cells in the peripheral blood of healthy individuals, tumor-infiltrating FOXP3(+)CD4 T cells, unlike FOXP3(-) T cells, were unable to produce IL-2 and IFN-gamma upon ex vivo stimulation, indicating that FOXP3 expression is a valid biological marker for human T(reg) cells even in the tumor microenvironment. Accordingly, we enumerated FOXP3(+)CD4 T(reg) cells in intratumoral and peritumoral sections of metastatic melanoma tumors and found a significant increase in proportion of FOXP3(+)CD4 T(reg) cells in the intratumoral compared with peritumoral areas. Moreover, their frequencies were 3- to 5-fold higher in tumors than in peripheral blood from the same patients or healthy donors, respectively. These findings demonstrate that the tumor-infiltrating CD4 T(reg) cell population is accurately depicted by FOXP3 expression, they selectively accumulate in tumors, and their frequency in peripheral blood does not properly reflect tumor microenvironment.

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