Repression of interleukin-2 mRNA translation in primary human breast carcinoma tumor-infiltrating lymphocytes

Cell Immunol. 1998 Dec 15;190(2):141-55. doi: 10.1006/cimm.1998.1390.

Abstract

Human breast carcinoma tumor-infiltrating lymphocytes (TIL) express activation antigens in situ indicative of ongoing immune response-CD28, CD45RO, CD69, CD71, and DR. However, interleukin 2 (IL-2) receptor was poorly expressed: CD25 was detected in only 1/24 samples and CD122 in only 2/24 samples. Furthermore, isolated breast cancer TIL were defective in proliferative response but recover when treated with recombinant IL-2. Nineteen of 24 tumor samples expressed B7-1, B7-2, and CD28 protein, showing that absence of costimulator proteins or counter ligand was not the basis for TIL proliferative deficit. Expression of IL-2 activity was not detected; however, mRNA encoding IL-2 was produced and translatable in vitro. These findings show that human breast cancer tumor-induced repression of IL-2 RNA translation is the basis of failure of TIL to express the IL-2 receptor and subsequent T cell hyporesponsiveness.

Publication types

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

MeSH terms

  • Breast Neoplasms / metabolism*
  • Female
  • Gene Expression Regulation
  • Humans
  • Interleukin-2 / biosynthesis*
  • Interleukin-2 / genetics
  • Lymphocytes, Tumor-Infiltrating / metabolism*
  • Protein Biosynthesis*
  • RNA, Messenger
  • Receptors, Interleukin-2 / genetics
  • Tumor Cells, Cultured

Substances

  • Interleukin-2
  • RNA, Messenger
  • Receptors, Interleukin-2