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

• Published in: Cancer Immunology, Immunotherapy Vol. 45; no. 1; pp. 20 - 28
• Main Authors: MULLINS, D. W, WALKER, T. M, BURGER, C. J, ELGERT, K. D
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01.10.1997; Springer Nature B.V; Springer-Verlag
• Subjects: Animals; Antineoplastic agents; Antineoplastic Agents, Phytogenic - pharmacology; Antitumor activity; Antitumor agents; Biological and medical sciences; Cell Division - physiology; Chemotherapy; Cytotoxicity; Cytotoxicity, Immunologic; Effector cells; Fibrosarcoma; Fibrosarcoma - drug therapy; Fibrosarcoma - immunology; Immune Tolerance - drug effects; Immunosuppression; Immunosuppressive agents; Isoantigens - immunology; Lymphocyte Activation - drug effects; Lymphocytes T; Macrophage Activation - drug effects; Macrophages; Macrophages - drug effects; Macrophages - immunology; Macrophages - metabolism; Male; Medical sciences; Mice; Mice, Inbred BALB C; Nitric oxide; Nitric Oxide - biosynthesis; Original; Paclitaxel; Paclitaxel - pharmacology; Pharmacology. Drug treatments; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; Tumor necrosis factor-α; γ-Interferon; Antineoplastic agent; Fibrosarcoma; Activation; Experimental study; In vitro; Immunotherapy; Taxane derivatives; T-Lymphocyte; Paclitaxel; Biological effect; Mechanism of action; Tumor cell; Macrophage
• ISSN: 0340-7004; 1432-0851
• DOI: 10.1007/s002620050396

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 gamma (IFN gamma)-primed murine normal host macrophages. We reported that tumor-distal macrophages, which mediate immunosuppression through dysregulated nitric oxide (NO) and tumor necrosis factor alpha (TNF alpha) 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 antitumor 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.