Repression of interleukin-2 mRNA translation in primary human breast carcinoma tumor-infiltrating lymphocytes.
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.
Lopez
C B
CB
Department of Surgery, Duke University School of Medicine, Durham, North Carolina, 27110, USA.
Rao
T D
TD
Feiner
H
H
Shapiro
R
R
Marks
J R
JR
Frey
A B
AB
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
D007376:Interleukin-2; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2