Loss of T-cell receptor-CD3zeta and T-cell function in tumor-infiltrating lymphocytes but not in tumor-associated lymphocytes in ovarian carcinoma

Surgery. 2001 Jun;129(6):749-56. doi: 10.1067/msy.2001.114554.


Background: Impaired T-cell function has been noted in tumor-infiltrating lymphocytes (TIL). Recently, loss of function was found to be associated with modifications in T-cell receptor complex (TCR)-mediated signaling. A common feature is loss or reduced expression levels of the signaling chain, TCRzeta. We evaluated whether loss of function in TIL and tumor-associated lymphocytes (TAL) from patients with ovarian cancer is associated with changes in TCRzeta expression, and which factors can cause these defects.

Methods: TIL and TAL were isolated from multiple patients and evaluated for their proliferative capacity by stimulation with a polyclonal stimulus. In addition, expression of TCRzeta and CD3epsilon was evaluated in fresh TIL and TAL by the Western blot technique. Finally, various conditions within a tumor environment were tested for their effect on TCRzeta and CD3epsilon.

Results: TIL, but not TAL, were significantly impaired in their proliferative response, even when both populations were derived from the same patient (P <.05). Reduced proliferation levels were associated with loss of expression of TCRzeta but not of CD3epsilon. Exposure of normal T cells to relative ischemia or heat shock, or culture in medium without IL-2, did not significantly reduce expression of TCRzeta compared with CD3epsilon. However, coculture of T cells with tumor-derived macrophages or tumor-derived factors led to a selective loss of TCRzeta compared with CD3epsilon (P <.05). Further analysis suggested that oxides such as hydrogen peroxide secreted by macrophages may be responsible for loss of TCRzeta and high molecular weight factors secreted by certain tumors.

Conclusions: TIL but not TAL show impaired T-cell function, which is associated with loss of TCRzeta. In addition to macrophages secreting oxides, loss of TCRzeta may be caused by tumor-derived soluble factors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Female
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Lymphocyte Activation
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Macrophages / physiology
  • Membrane Proteins / analysis*
  • Ovarian Neoplasms / immunology*
  • Receptors, Antigen, T-Cell / analysis*
  • T-Lymphocytes / immunology*
  • Tumor Cells, Cultured


  • Membrane Proteins
  • Receptors, Antigen, T-Cell
  • antigen T cell receptor, zeta chain
  • Hydrogen Peroxide