title: Repression of interleukin-2 mRNA translation in primary human breast carcinoma tumor-infiltrating lymphocytes.
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.
authors.affiliation: Department of Surgery, Duke University School of Medicine, Durham, North Carolina, 27110, USA.
authors.forename: C B
authors.initials: CB
authors.lastname: Lopez
authors.forename: T D
authors.initials: TD
authors.lastname: Rao
authors.forename: H
authors.initials: H
authors.lastname: Feiner
authors.forename: R
authors.initials: R
authors.lastname: Shapiro
authors.forename: J R
authors.initials: JR
authors.lastname: Marks
authors.forename: A B
authors.initials: AB
authors.lastname: Frey
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism*; D014176:Protein Biosynthesis; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2 / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: D007376:Interleukin-2; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2