Breast cancer-associated antigen, DF3/MUC1, induces apoptosis of activated human T cells
Breast cancer-associated antigen, DF3/MUC1, induces apoptosis of activated human T cells
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DOI：
10.1038/nm1296-1367
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发表时间：
1996-12-01
期刊：
影响因子：
82.9
通讯作者：
Nadler, LM
中科院分区：
文献类型：
--
作者：
Gimmi, CD;Morrison, BW;Nadler, LM
考虑到在人类中存在大量的乳腺癌相关抗原，包括MAGE-1、-2和-3、突变的p53、p21ras、HER-2/neu和DF3/MUC-1，再加上有证据表明存在针对这些抗原的体液和细胞毒性T细胞反应(1-6)，肿瘤免疫学家面临的中心困境是为什么宿主免疫反应如此低效。一种可能性是，肿瘤细胞本身要么是无效的，要么是无效的抗原提呈细胞(APC)。肿瘤细胞不能发挥APC的功能可能是由于它们不能处理和呈递抗原，缺乏或数量不足的黏附和共刺激分子，或者潜在地，分泌抑制性细胞因子。因此，我们试图确定人乳腺癌细胞系是否可以作为APC发挥作用，如果不能，则确定导致这一缺陷的机制(S)。在这里，我们展示了人类乳腺癌细胞株不能呈递同种异体抗原。这一缺陷并不在于它们固有的提呈抗原的能力，而是由于暴露于乳腺癌相关粘蛋白抗原DF3/MUC1诱导激活的T细胞凋亡。这些结果支持这样的假设，即DF3/MUC1可能与临床上有意义的抗癌特异性免疫反应的缺乏有关。
Given the plethora of well-documented breast carcinoma-associated antigens in humans including MAGE-1, -2 and -3, mutated p53, p21ras, HER-2/neu and DF3/MUC-1, coupled with evidence that humoral and cytotoxic T-cell responses against these antigens exist(1-6), the central dilemma facing tumor immunologists is why the host immune response is so inefficient. One possibility is that tumor cells themselves are either inefficient or ineffective antigen-presenting cells (APCs). The failure of tumor cells to function as APCs may be due to their inability to process and present the antigen, the absence or insufficient numbers of adhesion and costimulatory molecules or, potentially, the secretion of inhibitory cytokines. Therefore, we sought to determine whether human breast cancer cell lines could function as APCs and, if not, to identify mechanism(s) responsible for this defect. Here, we show that human breast cancer cell lines fail to present alloantigen. This defect does not reside in their inherent capacity to present antigen but rather is due to apoptosis of activated T cells induced by exposure to the breast carcinoma-associated mucin antigen, DF3/MUC1. These results support the hypothesis that DF3/MUC1 may contribute to the paucity of clinically significant anticarcinoma-specific immune responses.