FOXP3 expression accurately defines the population of intratumoral regulatory T cells that selectively accumulate in metastatic melanoma lesions

Mojgan Ahmadzadeh, Aloisio Felipe-Silva, Bianca Heemskerk, Daniel J. Powell, John R. Wunderlich, Maria J. Merino, Steven A. Rosenberg

Research output: Contribution to journalArticle

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-γ upon ex vivo stimulation, indicating that FOXP3 expression is a valid biological marker for human T reg cells even in the tumor microen-vironment. 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.

Original languageEnglish (US)
Pages (from-to)4953-4960
Number of pages8
JournalBlood
Volume112
Issue number13
DOIs
StatePublished - Dec 15 2008

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Ahmadzadeh, M., Felipe-Silva, A., Heemskerk, B., Powell, D. J., Wunderlich, J. R., Merino, M. J., & Rosenberg, S. A. (2008). FOXP3 expression accurately defines the population of intratumoral regulatory T cells that selectively accumulate in metastatic melanoma lesions. Blood, 112(13), 4953-4960. https://doi.org/10.1182/blood-2008-06-163048