Differential impairment of regulatory T cells rather than effector T cells by paclitaxel-based chemotherapy.
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-gamma 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.
Zhang
Lei
L
Department of Immunology of Shanghai Medical College and Institute for Immunobiology, Key Laboratory of Molecular Medicine of Ministry of Education, Fudan University, Shanghai, People's Republic of China.
Dermawan
Kamtai
K
Jin
Meilin
M
Liu
Rongjun
R
Zheng
Huiru
H
Xu
Lin
L
Zhang
Yi
Y
Cai
Yuchan
Y
Chu
Yiwei
Y
Xiong
Sidong
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000276:immunology; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D008175:Lung Neoplasms / Q000188:drug therapy / Q000276:immunology; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects*; D019014:fas Receptor / Q000096:biosynthesis
D000972:Antineoplastic Agents, Phytogenic; D007376:Interleukin-2; D019014:fas Receptor; D007371:Interferon-gamma; D017239:Paclitaxel