J.
Cancer Mol. 3: 55-60, 2007
[Research
Paper]
Dendritic Cells Pulsed with Irradiated Prostate Tumor Cells Express CC
Receptor-7 and Its Ligands and Initiate a Tumor Specific Immune Response
1Prabir
K. Chakravarty, Giridhar R. Gorla, Zoya Niazova, and Bhadrasain Vikram
Department of Radiation Oncology, Albert Einstein College of Medicine,
Bronx, NY, USA [P. K. Chakravarty, Z. Niazova, B. Vikram]; Department of
Radiation Oncology, Montefiore Medical Center, Bronx, NY, USA
[G. R. Gorla, B. Vikram]
Abstract:
AIM:
Dendritic cells (DCs) are potent antigen-presenting cells that play a
pivotal role in regulating immune response in cancer. This study is to
address whether irradiated prostate cancer cells have the capability to
induce DCs to respond against a tumor.
METHODS:
A highly tumorigenic mouse prostate tumor cell line RM-1 was subjected
to gamma-irradiation and tested for induction of apoptosis by exploiting
DNA analysis and Hoechst staining. Various in vitro experiments
were carried out to ascertain whether the irradiated tumor cells could
activate DCs, and whether the DCs pulsed with irradiated tumor cells
could stimulate splenocytes obtained from naïve C57BL/6J animals.
RESULTS:
Irradiation (10 and 60 Gy) caused apoptosis in RM-1 cells and DCs were
able to preferentially take up irradiated RM-1 cells. The irradiated
RM-1 cells were immunostimulatory even at comparatively low
stimulator/responder ratios as determined by co-culture experiments. By
contrast, non-irradiated tumor cells were unable to stimulate comparable
response. Moreover, the DCs pulsed with irradiated RM-1 cells could
express high amounts of CCR-7 and its ligands, CCL-19 and CCL-21. The
splenocytes when stimulated with these activated DCs showed significant
cytotoxic activity against fresh RM-1 cells, and they also secreted high
levels of interferon-gamma and interleukin-12.
CONCLUSION:
This is the first demonstration that irradiated prostate tumor cells can
activate DCs and these DCs express CCR-7 and its ligands, CCL-19 and
CCL-21. The activated DCs are further capable of stimulating
splenocytes of naïve animals. These results have potential implications
in designing effective DC-based immunotherapeutic strategy for prostate
cancer treatment.
(Keywords:
RM-1; irradiation; dendritic cell; CCR-7; immune response)
Received 1/4/07; Revised
3/12/07; Accepted 3/14/07.
1Correspondence:
Dr. Prabir K Chakravarty, c/o Dr. Diana Casper, Department of
Neurosurgery, Moses Room #310, Moses Research Pavilion, Montefiore
Medical Center, 111E 210th Street, Bronx, NY 10467, USA. Fax:
1-718-6533284. E-mail:
prabir9p@yahoo.com
2Abbreviations:
DCs, dendritic
cells; APCs, antigen-presenting cells; CTLs, cytotoxic T-lymphocytes;
MHC, major histocompatibility complex; RT, radiation therapy; IL,
interleukin; IFN, interferon; Th1, type-1 helper T cell.
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