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Treatment
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Stem Cells
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Cancer
Research, 66, 2630-2638, March 1, 2006
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Abstract |
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Interleukin-23–Expressing Bone
Marrow–Derived Neural Stem-Like Cells Exhibit Antitumor Activity
against Intracranial Glioma
Xiangpeng Yuan1,
Jinwei Hu1, Maria
L. Belladonna2, Keith
L. Black1 and John
S. Yu1
1Maxine Dunitz
Neurosurgical Institute, Cedars-Sinai Medical Center, Los Angeles,
California and 2Department of Experimental Medicine,
University of Perugia, Perugia, Italy. Requests for reprints: John S. Yu,
Maxine Dunitz Neurosurgical Institute, Cedars-Sinai Medical Center,
Suite 800 East, 8631 W. 3rd Street, Los Angeles, CA 90048.
Phone: 310-423-0845; E-mail: yuj@cshs.org.
Received 5/16/05; revised 12/ 9/05; accepted 12/27/05.
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Neural progenitor-like cells have been
isolated from bone marrow and the cells have the ability of
tracking intracranial tumor.
However, the capacity of the cells to
deliver molecules for activating immune response against
intracranial tumor and the identity of cellular and
molecular factors that are involved in such immune
responses have yet to be elucidated.
Here, we isolated neural
stem-like cells from the bone marrow of adult mice.
The isolated cells were capable of
producing progenies of three lineages, neurons, astrocytes,
and oligodendrocytes, in vitro and tracking glioma in
vivo.
By genetically manipulating bone
marrow–derived neural stem-like cells (BM-NSC) to express
a recently discovered cytokine, interleukin (IL)-23, the
cells showed protective effects in intracranial tumor-bearing C57BL/6
mice.
Depletion of subpopulation lymphocytes
showed that CD8+ T cells were critical for the
antitumor immunity of IL-23–expressing BM-NSCs and that
CD4+ T cells and natural killer (NK) cells
participated in the activity.
Furthermore, the
IL-23–expressing BM-NSC-treated survivors were resistant to
the same tumor rechallenge associated with enhanced IFN-γ, but
not IL-17, expression in the brain tissue.
Taken together, these data
suggest that IL-23–expressing BM-NSCs can effectively induce
antitumor immunity against intracranial gliomas. CD8+ T
cells are critical for such antitumor activity; in addition, CD4+
T cells and NK cells are also involved.
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© 2006 American Association for Cancer
Research
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Source: http://cancerres.aacrjournals.org/cgi/content/abstract/66/5/2630
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HTML
Full Text: http://cancerres.aacrjournals.org/cgi/content/full/66/5/2630
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PDF
Full Text: http://cancerres.aacrjournals.org/cgi/reprint/66/5/2630
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