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Taxol-mediated changes in fibrosarcoma-induced immune cell function: Modulation of antitumor activities

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Abstract

The anticancer drug taxol (paclitaxel) inhibits tumors through multiple cytotoxic and cytostatic mechanisms. Independently of these mechanisms, taxol induces distinct immunological efficacy when it acts as a second signal for activation of tumoricidal activity by interferon-γ(IFNγ)-primed murine normal host macrophages. We reported that tumor-distal macrophages, which mediate immunosuppression through dysregulated nitric oxide (NO) and tumor necrosis factor α (TNFα) production, are differentially regulated by taxol. Because taxol influences tumor cell growth dynamics and activates immune cell populations, we assessed the ex vivo immunosuppressive and antitumor activities of taxol-treated normal host and tumor-bearing host (TBH) macrophages. Pretreatment of such cells with taxol partly reconstituted T cell alloantigen reactivity, suggesting that taxol mediates a limited reversal of TBH macrophage immunosuppressive activity. Taxol-treated TBH macrophages significantly suppressed the growth of fibrosarcoma cells (Meth-KDE) through soluble effector molecules and promoted direct cell-mediated cytotoxicity, indicating that taxol enhanced tumor-induced macrophage antitumor activities. Tumor-induced helper T cells, however, showed a higher sensitivity to direct taxol-induced suppression. These data demonstrate that taxol exerts pleiotropic effects on antitumor immune responses with the capacity to abate the immunosuppressive activities of macrophages and promote macrophage-mediated anti-tumor activities simultaneously, but also directly modulating T cell reactivity. Collectively, these studies suggest that the antineoplastic drug taxol may impart antitumor activity through an immunotherapeutic capacity.

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Author notes

  1. David W. Mullins

    Present address: Department of Biology, University of Central Arkansas, Lewis Science Center, 72035-0001, Conway, AR, USA

Authors and Affiliations

  1. Department of Biology, Microbiology and Immunology Section, Virginia Polytechnic Institute and State University, 24061-0406, Blacksburg, VA, USA

    David W. Mullins, Thomas M. Walker, Carol J. Burger & Klaus D. Elgert

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  1. David W. Mullins
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  2. Thomas M. Walker
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  3. Carol J. Burger
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  4. Klaus D. Elgert
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Correspondence to Klaus D. Elgert.

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Mullins, D.W., Walker, T.M., Burger, C.J. et al. Taxol-mediated changes in fibrosarcoma-induced immune cell function: Modulation of antitumor activities. Cancer Immunol Immunother 45, 20–28 (1997). https://doi.org/10.1007/s002620050396

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  • DOI: https://doi.org/10.1007/s002620050396

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