來自Virginia Commonwealth大學(xué)Massey腫瘤中心的科學(xué)家最近在研究免疫系統(tǒng)和癌細(xì)胞之間的關(guān)系時發(fā)現(xiàn),，γ干擾素是癌癥復(fù)發(fā)過程中一種重要的信號蛋白。他們的結(jié)果發(fā)表在3月份的歐洲免疫學(xué)會官方刊物《European Journal of Immunology》上,。
這一結(jié)果很可能幫助科學(xué)家找到對付多種癌癥的疫苗或免疫學(xué)治療手段——通過操縱免疫系統(tǒng)來識別和根除癌癥細(xì)胞,。
利用一種患有乳腺癌的轉(zhuǎn)基因老鼠模型,，科學(xué)家發(fā)現(xiàn)γ干擾素——免疫系統(tǒng)細(xì)胞被激活后產(chǎn)生的一種化學(xué)信使分子——在癌癥復(fù)發(fā)過程中起著重要作用,。在人體內(nèi)，當(dāng)我們受到病原體或者癌細(xì)胞入侵時,，免疫系統(tǒng)的白細(xì)胞就會產(chǎn)生這種γ干擾素,，從而幫助人類對抗感染。之前醫(yī)生普遍認(rèn)為,，淋巴細(xì)胞產(chǎn)生的γ干擾素是腫瘤治療預(yù)后良好的表現(xiàn),，但是新發(fā)現(xiàn)卻提出了相反的看法。
項目主要負(fù)責(zé)人Masoud H. Manjili博士表示：“通過了解癌癥復(fù)發(fā)的分子學(xué)機制,，我們就可以制造疫苗,，在病人體內(nèi)引入特定的免疫反應(yīng)，而不是像之前那樣引發(fā)大面積的免疫反應(yīng)——其中有一些可能會導(dǎo)致癌癥復(fù)發(fā),。我們的最終目標(biāo)是,，找到一種多肽疫苗，能在不造成HER-2/neu蛋白損失情況下引起癌細(xì)胞死亡,。HER-2/neu損失是癌細(xì)胞用來逃避免疫破壞的機制,。”
從2000年開始，Manjili和同事就開始在患有乳腺癌的動物身上測試疫苗的有效性,。這種疫苗包含一種HSP110蛋白,，它作為輔助的催化劑，以及癌細(xì)胞抗原HER-2/neu,。
譯自：physorg.com
部分英文原文：
Cellular immune response
HER-2/neu antigen loss and relapse of mammary carcinoma are actively induced by T cell-mediated anti-tumor immune responses
Maciej Kmieciak 1, Keith L. Knutson 2, Catherine I. Dumur 3, Masoud H. Manjili 1 *
1Department of Microbiology & Immunology , VCU School of Medicine, Massey Cancer Center, Richmond, VA
2Department of Immunology, Mayo Clinic College of Medicine, Rochester, MN
3Department of Pathology, VCU School of Medicine, Massey Cancer Center, Richmond, VA
email: Masoud H. Manjili ([email protected])
*Correspondence to Masoud H. Manjili, Department of Microbiology & Immunology, VCU School of Medicine, Massey Cancer Center, Box 980035, 401 College Street, Richmond, VA 23298, USA, Fax: +1-804-828-8453
Funded by:
National Institutes of Health (NIH); Grant Number: R01 CA104757, P30CA16059
Susan G. Komen Foundation for Breast Cancer Research; Grant Number: BCTR0504184
Keywords
Cytokines ?Immune evasion ?Tumor immunology
Abstract
Induction of tumor-specific immune responses results in the inhibition of tumor development. However, tumors recur because of the tumor immunoediting process that facilitates development of escape mechanisms in tumors. It is not known whether tumor escape is an active process whereby anti-tumor immune responses induce loss or downregulation of the target antigen in the antigen-positive clones. To address this question, we used rat neu-overexpressing mouse mammary carcinoma (MMC) and its relapsed neu antigen-negative variant (ANV). ANV emerged from MMC under pressure from neu-specific T cell responses in vivo. We then cloned residual neu antigen-negative cells from MMC and residual neu antigen-positive cells from ANV. We found marked differences between these neu-negative clones and ANV, demonstrating that the residual neu-negative clones are probably not the origin of ANV. Since initial rejection of MMC was associated with the presence of IFN--secreting T cells, we treated MMC with IFN- and showed that IFN- could induce downregulation of neu expression in MMC. This appears to be due to methylation of the neu promoter. Together, these data suggest that neu antigen loss is an active process that occurs in primary tumors due to the neu-targeted anti-tumor immune responses.
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Received: 30 August 2006; Revised: 13 December 2006; Accepted: 18 January 2007
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