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Monocytes promote tumor cell survival in T-cell lymphoproliferative disorders and are impaired in their ability to differentiate into mature dendritic cells
- Source :
- Blood. 114:2936-2944
- Publication Year :
- 2009
- Publisher :
- American Society of Hematology, 2009.
-
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.
- Subjects :
- Stromal cell
Cell Survival
T-Lymphocytes
T cell
Immunology
Antigen presentation
Mice, SCID
Biology
Lymphoma, T-Cell
Biochemistry
Monocytes
Immunoenzyme Techniques
Mice
Mice, Inbred NOD
medicine
Animals
Humans
Antigen-presenting cell
Chemokine CCL5
Antigen Presentation
Tumor microenvironment
Lymphoid Neoplasia
Monocyte
Autologous Monocytes
Cell Differentiation
Dendritic Cells
Cell Biology
Hematology
Dendritic cell
Flow Cytometry
Xenograft Model Antitumor Assays
Interleukin-10
medicine.anatomical_structure
Subjects
Details
- ISSN :
- 15280020 and 00064971
- Volume :
- 114
- Database :
- OpenAIRE
- Journal :
- Blood
- Accession number :
- edsair.doi.dedup.....74fa4583398e646667a46edc74706133
- Full Text :
- https://doi.org/10.1182/blood-2009-05-220111