Erlotinib inhibits T-cell-mediated immune response via down-regulation of the c-Raf/ERK cascade and Akt signaling pathway

Journal Article · Tue Mar 01 00:00:00 EST 2011 · Toxicology and Applied Pharmacology

OSTI ID:21535243

Qiong, Luo ^[1]; Yanhong, Gu ^[2]; Wei, Zheng; Xingxin, Wu; Fangyuan, Gong; Liyun, Gu; Yang, Sun ^[1]

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1. State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University 22 Han Kou Road, Nanjing 210093 (China)
2. Department of Clinical Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029 (China)

Erlotinib is a potent inhibitor of epidermal growth factor receptor tyrosine kinase and has been demonstrated to treat advanced or metastatic non-small cell lung cancer to prolong survival after failure of first-line or second-line chemotherapy. However, little is known about its effects on immune system. In the present study, we aimed to investigate the immunosuppressive activity of erlotinib on T lymphocytes both in vitro and in vivo, and further explore its potential molecular mechanism. Erlotinib exerted a significant inhibition on the T cell proliferation and activation induced by concanavalin A, anti-CD3 plus anti-CD28, staphylococcal enterotoxin B or phorbol myristate acetate respectively in a concentration-dependent manner and it also inhibited the secretion of the proinflammatory cytokines such as IL-2 and IFN-{gamma} of activated T cells. Further study showed that erlotinib caused G0/G1 arrest and suppressed the phosphorylations of c-Raf, ERK and Akt in activated T cells. Moreover, erlotinib significantly ameliorated picryl chloride-induced ear contact dermatitis in a dose-dependent manner in vivo. In summary, these findings suggest that erlotinib may cause the impairment of T-cell-mediated immune response both in vitro and in vivo through inhibiting T cell proliferation and activation, which is closely associated with its potent down-regulation of the c-Raf/ERK cascade and Akt signaling pathway. - Graphical abstract: Erlotinib may cause the impairment of T-cell-mediated immune response both in vitro and in vivo through inhibiting T cell proliferation and activation, which is closely associated with its potent down-regulation of the c-Raf/ERK cascade and Akt signaling pathway. Display Omitted

• OSTI ID: 21535243
• Journal Information: Toxicology and Applied Pharmacology, Vol. 251, Issue 2; Other Information: DOI: 10.1016/j.taap.2010.12.011; PII: S0041-008X(10)00468-0; Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CELL PROLIFERATION
CHEMOTHERAPY
CONCANAVALIN A
IMMUNOSUPPRESSION
IN VITRO
IN VIVO
INHIBITION
LYMPHOCYTES
LYMPHOKINES
METASTASES
NEOPLASMS
PHOSPHORYLATION
REGULATIONS
TYROSINE
AGGLUTININS
AMINO ACIDS
ANIMAL CELLS
ANTIBODIES
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CARBOXYLIC ACIDS
CHEMICAL REACTIONS
CONNECTIVE TISSUE CELLS
DISEASES
GROWTH FACTORS
HEMAGGLUTININS
HYDROXY ACIDS
LAWS
LECTINS
LEUKOCYTES
MATERIALS
MEDICINE
MITOGENS
ORGANIC ACIDS
ORGANIC COMPOUNDS
PROTEINS
SOMATIC CELLS
THERAPY