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

Toxicol Appl Pharmacol. 2011 Mar 1;251(2):130-6. doi: 10.1016/j.taap.2010.12.011. Epub 2010 Dec 31.


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-γ 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Down-Regulation / drug effects*
  • Down-Regulation / immunology
  • Erlotinib Hydrochloride
  • Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors*
  • Extracellular Signal-Regulated MAP Kinases / physiology
  • Female
  • MAP Kinase Signaling System / drug effects*
  • MAP Kinase Signaling System / immunology
  • Mice
  • Mice, Inbred BALB C
  • Oncogene Protein v-akt / antagonists & inhibitors*
  • Oncogene Protein v-akt / physiology
  • Protein Kinase Inhibitors / toxicity*
  • Proto-Oncogene Proteins c-raf / antagonists & inhibitors*
  • Quinazolines / toxicity*
  • T-Lymphocyte Subsets / drug effects*
  • T-Lymphocyte Subsets / immunology


  • Protein Kinase Inhibitors
  • Quinazolines
  • Erlotinib Hydrochloride
  • Oncogene Protein v-akt
  • Proto-Oncogene Proteins c-raf
  • Extracellular Signal-Regulated MAP Kinases