Abstract Book 2010 - CIMT Annual Meeting

107 Sevko | Enhancing immunity & adjuvants
Paclitaxel in ultra-low doses reduces immunosuppression
in ret transgenic tumor bearing mice
Alexandra Sevko 1 , Michael Shurin 2 , Viktor Umansky 1
1 German Cancer Research Center, Heidelberg, Germany
2 Departments of Pathology and Immunology, University of Pittsburgh Medical Center, Pittsburgh,
Pennsylvania, USA
It has been recently shown that chemotherapeutic
drugs such as paclitaxel, 5-fluoruracil or doxorubicin
applied in ultra-low, noncytotoxic doses stimulate
dendritic cell activity, and induce antitumor
immune responses in mouse transplantable tumor
models.
We studied effects of ultra low-dose paclitaxel on
tumor progression in ret transgenic mouse model
of spontaneous melanoma, which closely resembles
human melanoma regarding histopathology and
clinical development.
We showed that the survival of melanoma bearing
mice upon the treatment was significantly increased
as compared to non-treated group that correlated
with a significant decrease in the tumor weight
in mice from paclitaxel-treated group. To evaluate
the mechanism of this antitumor effect, we focused
on immunosuppressive cells like myeloid derived
suppressor cells (MDSC) and regulatory T cells
(Treg). Paclitaxel was found to decrease the number
of MDSC infiltrating primary tumors and metastatic
lymph nodes. Importantly, the amount of MDSC producing
immunosuppressive agent nitric oxide was
also decreased in these melanoma lesions and in the
bone marrow. In addition, paclitaxel induced a reduction
of Treg infiltrating primary tumors without
affecting the total number of CD4+ T cells.
We suggest that ultra low-dose paclitaxel therapy
can neutralize tumor-induced immune suppression
leading to the delayed tumor progression and prolonged
survival of tumor bearing mice.
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