研究发现癌症复发和γ干扰素有关

生物谷

    来自Virginia  Commonwealth大学Massey肿瘤中心的科学家最近在研究免疫系统和癌细胞之间的关系时发现，γ干扰素是癌症复发过程中一种重要的信号蛋白。他们的结果发表在3月份的欧洲免疫学会官方刊物《European  Journal  of  Immunology》上。
    这一结果很可能帮助科学家找到对付多种癌症的疫苗或免疫学治疗手段——通过操纵免疫系统来识别和根除癌症细胞。
    利用一种患有乳腺癌的转基因老鼠模型，科学家发现γ干扰素——免疫系统细胞被激活后产生的一种化学信使分子——在癌症复发过程中起着重要作用。在人体内，当我们受到病原体或者癌细胞入侵时，免疫系统的白细胞就会产生这种γ干扰素，从而帮助人类对抗感染。之前医生普遍认为，淋巴细胞产生的γ干扰素是肿瘤治疗预后良好的表现，但是新发现却提出了相反的看法。
    项目主要负责人Masoud  H.  Manjili博士表示：“通过了解癌症复发的分子学机制，我们就可以制造疫苗，在病人体内引入特定的免疫反应，而不是像之前那样引发大面积的免疫反应——其中有一些可能会导致癌症复发。我们的最终目标是，找到一种多肽疫苗，能在不造成HER-2/neu蛋白损失情况下引起癌细胞死亡。HER-2/neu损失是癌细胞用来逃避免疫破坏的机制。”
    从2000年开始，Manjili和同事就开始在患有乳腺癌的动物身上测试疫苗的有效性。这种疫苗包含一种HSP110蛋白，它作为辅助的催化剂，以及癌细胞抗原HER-2/neu。

    译自：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 (mmanjili@vcu.edu)

*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.

Received: 30 August 2006; Revised: 13 December 2006; Accepted: 18 January 2007

Digital Object Identifier (DOI)