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

Repression of interleukin-2 mRNA translation in primary human breast carcinoma tumor-infiltrating lymphocytes
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DOI:
10.1006/cimm.1998.1390
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发表时间:
1998-12-15
影响因子:
4.3
通讯作者:
Frey, AB
Frey, AB
中科院分区:
医学4区
文献类型:
--
作者:
Lopez, CB;Rao, TD;Frey, AB

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人乳腺癌肿瘤浸润淋巴细胞 (TIL) 原位表达激活抗原,表明正在进行的免疫反应 - CD28、CD45RO、CD69、CD71 和 DR。然而,白介素 2 (IL-2) 受体表达较差:仅在 1/24 个样本中检测到 CD25,仅在 2/24 个样本中检测到 CD122。此外,分离的乳腺癌TIL在增殖反应中存在缺陷,但在用重组IL-2治疗后恢复。24个肿瘤样本中的19个表达B7-1、B7-2和CD28蛋白,表明共刺激蛋白或反配体的缺乏并不是TIL增殖缺陷的基础。未检测到IL-2活性表达;然而,编码 IL-2 的 mRNA 是在体外产生并可翻译的。这些发现表明,人乳腺癌肿瘤诱导的 IL-2 RNA 翻译抑制是 TIL 无法表达 IL-2 受体和随后 T 细胞反应低下的基础,(C) 1998 年学术出版社。
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, (C) 1998 Academic Press.