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Research Paper

Gemcitabine Has Significant Immunomodulatory Activity in Murine Tumor Models Independent of its Cytotoxic Effects

Eiji Suzuki, Jing Sun, Veena Kapoor, Arminder S Jassar and Steven M. Albelda

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Given reports that the chemotherapeutic agent gemcitabine (GEM) does not block T-lymphocyte recall responses and is not detrimental to specific anti-tumor immunity, studies to evaluate the use of GEM in combination with immunotherapy were initiated. When we tested the therapeutic effects of GEM as a single agent in various murine tumor models, we found that a single dose of GEM had impressive anti-tumor activity in a specific subset of tumors. Surprisingly, efficacy was not related to in vitro drug sensitivity, but instead, correlated with the immunogenicity of the tumor. A key role of the immune system in GEM’s action was demonstrated in experiments showing that the anti-tumor effects of GEM were lost in nude mice. In addition, we saw equivalent anti-tumor effects of GEM in animals bearing tumors that were extremely resistant to the in vitro cytotoxic effects of GEM versus parental GEM-sensitive cells. This therapeutic efficacy was thus not due to direct cytotoxic effect on tumor cells, but rather to an enhancement of T-cell mediated anti-tumor immune effects. These data raise the exciting possibility that GEM may be a useful agent in combination with various types of tumor immunotherapy.

This is an open-access article

 Download PDF

If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.