Selective depletion of regulatory T cell subsets by docetaxel treatment in patients with nonsmall cell lung cancer.

Abstract

Regulatory T (Treg) cells are potent suppressors that maintain immune homeostasis. Accumulation of Treg can inhibit effective immune responses in cancer patients, leading to tumor development and progression. Despite direct cytotoxicity, several chemotherapeutic drugs have been reported to deplete Treg cells for better prognosis for cancer patients. Treg cells are a heterogenous population with at least three different subsets, nonsuppressive, resting, and activated Treg cells. However, the characteristics of Treg cell subsets in lung cancer patients and how chemotherapy affects Treg cells remain elusive. In this study, we first analyzed Treg cell subsets in peripheral blood samples from 40 nonsmall cell lung cancer (NSCLC) patients and 20 healthy donors. Treg cells, specifically activated Treg cell subset, significantly increased in patients with NSCLC. Compared to nonsuppressive Treg cells, activated Treg cells expressed higher level of CD39 and predominantly produced inhibitory cytokines. In vitro assay showed that docetaxel reduced all three subsets of Treg cells. More importantly, we found docetaxel-based chemotherapy significantly decreased all three Treg subsets after 4 cycles of treatment in 17 NSCLC patients. Taken together, this study revealed dynamic changes of various Treg cell subsets in NSCLC patients before and after chemotherapy, providing activated Treg cells as a potential target for chemotherapy.

• Authors: Jie-Yao Li, Xiu-Fang Duan, Li-Ping Wang, Yu-Jie Xu, Lan Huang, Teng-Fei Zhang, Jin-Yan Liu, Feng Li, Zhen Zhang, Dong-Li Yue, Fei Wang, Bin Zhang, Yi Zhang
• Journal: Journal of immunology research (J Immunol Res) Vol. 2014 Pg. 286170 ( 2014) ISSN: 2314-7156 [Electronic] Egypt
• PMID: 24868562 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• Taxoids
• Docetaxel

Topics

• Aged
• Antineoplastic Agents, Phytogenic (therapeutic use)
• Carcinoma, Non-Small-Cell Lung (drug therapy, immunology, pathology)
• Case-Control Studies
• Cell Lineage (immunology)
• Docetaxel
• Female
• Humans
• Immunophenotyping
• Lung Neoplasms (drug therapy, immunology, pathology)
• Lymphocyte Depletion
• Male
• Middle Aged
• Neoplasm Staging
• T-Lymphocytes, Regulatory (classification, drug effects, immunology, pathology)
• Taxoids (therapeutic use)