Street Shayna E A, Zerafa Nadeen, Iezzi Manuela, Westwood Jennifer A, Stagg John, Musiani Piero, Smyth Mark J
Cancer Immunology Program, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
Cancer Res. 2007 Jun 1;67(11):5454-60. doi: 10.1158/0008-5472.CAN-06-4084.
The concept of tumor immune surveillance has been supported by several recent studies in mice which show that immune effector mechanisms suppress hematologic malignancy. However, because the most common forms of human cancer are epithelial in origin, and comparatively very little data supports the immune surveillance of epithelial malignancies, we have chosen to evaluate the role of perforin-mediated cytotoxicity in the prevention of BALB/c Her2/neu-induced mammary cancer. Interestingly, perforin significantly delayed the onset of mammary tumorigenesis and reduced the number of mammary tumors without improving survival. Natural killer cell, but not CD8+ T cell, depletion resulted in a similar phenotype to perforin deficiency in this regard. Histologic analysis further indicated that the effect of perforin was most evident during the earliest stages of carcinogenesis rather than prior to or during the hyperplastic phase. This data suggests that perforin may mediate some suppression of epithelial carcinogenesis by intervening early in the tumor development process.
肿瘤免疫监视的概念已得到近期多项小鼠研究的支持，这些研究表明免疫效应机制可抑制血液系统恶性肿瘤。然而，由于人类最常见的癌症形式起源于上皮组织，且相对而言极少有数据支持上皮性恶性肿瘤的免疫监视，我们选择评估穿孔素介导的细胞毒性在预防BALB/c Her2/neu诱导的乳腺癌中的作用。有趣的是，穿孔素显著延迟了乳腺肿瘤发生的起始时间，并减少了乳腺肿瘤的数量，但并未提高生存率。在这方面，自然杀伤细胞而非CD8+ T细胞的耗竭导致了与穿孔素缺陷相似的表型。组织学分析进一步表明，穿孔素的作用在致癌作用的最早阶段最为明显，而非在增生期之前或期间。这些数据表明，穿孔素可能通过在肿瘤发展过程的早期进行干预来介导对上皮性致癌作用的某种抑制。
