Monocytes promote tumor cell survival in T-cell lymphoproliferative disorders and are impaired in their ability to differentiate into mature dendritic cells

Ryan A. Wilcox, David A. Wada, Steven C. Ziesmer, Sherine F. Elsawa, Nneka I. Comfere, Allan B Dietz, Anne J Novak, Thomas Elmer Witzig, Andrew L Feldman, Mark R. Pittelkow, Stephen Maxted Ansell

Research output: Contribution to journalArticle

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Abstract

A variety of nonmalignant cells present in the tumor microenvironment promotes tumorigenesis by stimulating tumor cell growth and metastasis or suppressing host immunity. The role of such stromal cells in T-cell lymphoproliferative disorders is incompletely understood. Monocyte-derived cells (MDCs), including professional antigen-presenting cells such as dendritic cells (DCs), play a central role in T-cell biology. Here, we provide evidence that monocytes promote the survival of malignant T cells and demonstrate that MDCs are abundant within the tumor microenvironment of T cell-derived lymphomas. Malignant T cells were observed to remain viable during in vitro culture with autologous monocytes, but cell death was significantly increased after monocyte depletion. Furthermore, monocytes prevent the induction of cell death in T-cell lymphoma lines in response to either serum starvation or doxorubicin, and promote the engraftment of these cells in nonobese diabetic/severe combined immunodeficient mice. Monocytes are actively recruited to the tumor microenvironment by CCL5 (RANTES), where their differentiation into mature DCs is impaired by tumor-derived interleukin-10. Collectively, the data presented demonstrate a previously undescribed role for monocytes in T-cell lymphoproliferative disorders.

Original languageEnglish (US)
Pages (from-to)2936-2944
Number of pages9
JournalBlood
Volume114
Issue number14
DOIs
StatePublished - 2009

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T-cells
Lymphoproliferative Disorders
Dendritic Cells
Tumors
Monocytes
Cell Survival
Cells
T-Lymphocytes
Tumor Microenvironment
Neoplasms
Cell death
T-Cell Lymphoma
Cytology
Cell Death
Chemokine CCL5
Cell growth
SCID Mice
Cell culture
Interleukin-10
Doxorubicin

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Monocytes promote tumor cell survival in T-cell lymphoproliferative disorders and are impaired in their ability to differentiate into mature dendritic cells. / Wilcox, Ryan A.; Wada, David A.; Ziesmer, Steven C.; Elsawa, Sherine F.; Comfere, Nneka I.; Dietz, Allan B; Novak, Anne J; Witzig, Thomas Elmer; Feldman, Andrew L; Pittelkow, Mark R.; Ansell, Stephen Maxted.

In: Blood, Vol. 114, No. 14, 2009, p. 2936-2944.

Research output: Contribution to journalArticle

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abstract = "A variety of nonmalignant cells present in the tumor microenvironment promotes tumorigenesis by stimulating tumor cell growth and metastasis or suppressing host immunity. The role of such stromal cells in T-cell lymphoproliferative disorders is incompletely understood. Monocyte-derived cells (MDCs), including professional antigen-presenting cells such as dendritic cells (DCs), play a central role in T-cell biology. Here, we provide evidence that monocytes promote the survival of malignant T cells and demonstrate that MDCs are abundant within the tumor microenvironment of T cell-derived lymphomas. Malignant T cells were observed to remain viable during in vitro culture with autologous monocytes, but cell death was significantly increased after monocyte depletion. Furthermore, monocytes prevent the induction of cell death in T-cell lymphoma lines in response to either serum starvation or doxorubicin, and promote the engraftment of these cells in nonobese diabetic/severe combined immunodeficient mice. Monocytes are actively recruited to the tumor microenvironment by CCL5 (RANTES), where their differentiation into mature DCs is impaired by tumor-derived interleukin-10. Collectively, the data presented demonstrate a previously undescribed role for monocytes in T-cell lymphoproliferative disorders.",
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AU - Wada, David A.

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AU - Elsawa, Sherine F.

AU - Comfere, Nneka I.

AU - Dietz, Allan B

AU - Novak, Anne J

AU - Witzig, Thomas Elmer

AU - Feldman, Andrew L

AU - Pittelkow, Mark R.

AU - Ansell, Stephen Maxted

PY - 2009

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N2 - A variety of nonmalignant cells present in the tumor microenvironment promotes tumorigenesis by stimulating tumor cell growth and metastasis or suppressing host immunity. The role of such stromal cells in T-cell lymphoproliferative disorders is incompletely understood. Monocyte-derived cells (MDCs), including professional antigen-presenting cells such as dendritic cells (DCs), play a central role in T-cell biology. Here, we provide evidence that monocytes promote the survival of malignant T cells and demonstrate that MDCs are abundant within the tumor microenvironment of T cell-derived lymphomas. Malignant T cells were observed to remain viable during in vitro culture with autologous monocytes, but cell death was significantly increased after monocyte depletion. Furthermore, monocytes prevent the induction of cell death in T-cell lymphoma lines in response to either serum starvation or doxorubicin, and promote the engraftment of these cells in nonobese diabetic/severe combined immunodeficient mice. Monocytes are actively recruited to the tumor microenvironment by CCL5 (RANTES), where their differentiation into mature DCs is impaired by tumor-derived interleukin-10. Collectively, the data presented demonstrate a previously undescribed role for monocytes in T-cell lymphoproliferative disorders.

AB - A variety of nonmalignant cells present in the tumor microenvironment promotes tumorigenesis by stimulating tumor cell growth and metastasis or suppressing host immunity. The role of such stromal cells in T-cell lymphoproliferative disorders is incompletely understood. Monocyte-derived cells (MDCs), including professional antigen-presenting cells such as dendritic cells (DCs), play a central role in T-cell biology. Here, we provide evidence that monocytes promote the survival of malignant T cells and demonstrate that MDCs are abundant within the tumor microenvironment of T cell-derived lymphomas. Malignant T cells were observed to remain viable during in vitro culture with autologous monocytes, but cell death was significantly increased after monocyte depletion. Furthermore, monocytes prevent the induction of cell death in T-cell lymphoma lines in response to either serum starvation or doxorubicin, and promote the engraftment of these cells in nonobese diabetic/severe combined immunodeficient mice. Monocytes are actively recruited to the tumor microenvironment by CCL5 (RANTES), where their differentiation into mature DCs is impaired by tumor-derived interleukin-10. Collectively, the data presented demonstrate a previously undescribed role for monocytes in T-cell lymphoproliferative disorders.

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