Gemcitabine has significant immunomodulatory activity in murine tumor models independent of its cytotoxic effects

  • Suzuki E
  • Sun J
  • Kapoor V
 et al. 
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Abstract

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. ©2007 Landes Bioscience.

Author-supplied keywords

  • [Chemotherapy, Cytotoxic T-lymphocyte, Gemcitabine

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Authors

  • E. Suzuki

  • J. Sun

  • V. Kapoor

  • A.S. Jassar

  • S.M. Albelda

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