Differential impairment of regulatory T cells rather than effector T cells by paclitaxel-based chemotherapy

• Published in: Clinical immunology (Orlando, Fla.) Fla.), 2008-11, Vol.129 (2), p.219-229
• Main Authors: Zhang, Lei, Dermawan, Kamtai, Jin, Meilin, Liu, Rongjun, Zheng, Huiru, Xu, Lin, Zhang, Yi, Cai, Yuchan, Chu, Yiwei, Xiong, Sidong
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Allergy and Immunology; Antineoplastic Agents, Phytogenic - pharmacology; Apoptosis - drug effects; Biological and medical sciences; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - immunology; Chemotherapy; fas Receptor - biosynthesis; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Interferon-gamma - biosynthesis; Interleukin-2 - biosynthesis; Lung Neoplasms - drug therapy; Lung Neoplasms - immunology; Male; Medical sciences; Middle Aged; Non-small cell lung cancer; Paclitaxel; Paclitaxel - pharmacology; Pneumology; Regulatory T cells; T-Lymphocytes - drug effects; T-Lymphocytes, Regulatory - drug effects; Tumors of the respiratory system and mediastinum
• ISSN: 1521-6616; 0090-1229; 1521-7035
• DOI: 10.1016/j.clim.2008.07.013

Abstract Characterized as a mitotic inhibitor, paclitaxel has gained importance as a promising agent for the treatment of advanced non-small cell lung cancer (NSCLC). However, whether paclitaxel has immune modulatory effects remains unclear. In this study, we analyzed 55 peripheral blood samples from NSCLC patients who underwent paclitaxel-based chemotherapy. We found that among the lymphocyte subsets, paclitaxel selectively decreased the size of the regulatory T cell (Treg) population rather than other subsets including effector T cells (Teff). Apoptosis by upregulating the expression of the cell death receptor Fas (CD95) contributed to the reduced cell number of Treg. Importantly, the inhibitory function of Treg was significantly impaired, while the production of Th1 cytokines IFN-γ and IL-2 and the expression of the activation marker CD44 among CD4+ and CD8+ T cells were augmented after paclitaxel treatment. These results strongly demonstrated that paclitaxel-based chemotherapy played important roles in modulating immune responses.