生物谷：美国Southern California大学的科学家最近表示，肿瘤最基本特征之一：如何躲避免疫系统攻击将成为癌细胞最大弱点。研究小组针对乳腺癌和直肠癌的研究证实，一种寻找癌症“免疫签名”的技术能有助于某些特定癌症的诊断和治疗。
在7月1日的《临床癌症研究》（Clinical Cancer Research）上，科学家描述了使用一种新技术来分析癌细胞中的基因变异，这使得它们可以躲避身体免疫系统的防御。科学家相信这一技术将成为癌症诊断和治疗的标准手段之一。
肿瘤细胞拥有多种基因和生物学变异。不同癌症之间这种差异非常明显，即使在同种癌症中也存在类似差别。但是尽管组成免疫签名的基因变异非常复杂，科学家还是发现了一小组基因在表达免疫学行为方面是完整的。
利用一种实时高速基因放大技术PCR，小组全面扫描了肿瘤，结果确认了肿瘤中14个促进免疫的基因和11个关键的对抗免疫的基因。小组还分析了老鼠中乳腺癌、白血病、肠癌、肺癌和肾癌中这些基因的表达。他们比较了其中2种免疫签名和相应的人类肿瘤的差异。
结果发现，人类乳腺癌的免疫签名和老鼠的符合得相当好。在所有病例中，科学家都发现了基因CD83和CD28被抑制，这是两个影响免疫细胞活性的基因。而基因B7-H4得到促进，它产生的蛋白能抑制免疫活性。而肠癌的免疫签名则有所变化，这意味着需要对每个病人进行分析。 （教育部科技发展中心)
原文链接：http://www.physorg.com/news102610745.html
原始出处:
Clinical Cancer Research 13, 4016-4025, July 1, 2007. doi: 10.1158/1078-0432.CCR-07-0016
Cancer Therapy: Preclinical
Immune Signatures of Murine and Human Cancers Reveal Unique Mechanisms of Tumor Escape and New Targets for Cancer Immunotherapy
Rebecca E. Sadun, Suzanne M. Sachsman, Xiaoying Chen, Kamilee W. Christenson, William Z. Morris, Peisheng Hu and Alan L. Epstein
Authors' Affiliation: Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California
Requests for reprints: Alan L. Epstein, Department of Pathology, University of Southern California, Keck School of Medicine, 2011 Zonal Avenue, HMR 205, Los Angeles, CA 90033. Phone: 323-442-1172; Fax: 323-342-3049; E-mail: aepstein@usc.edu .
Purpose: Despite lymphocyte infiltration of tumors and the activation of tumor-draining lymph nodes, malignant tumors are able to "escape" from both innate and adaptive immune responses. For immunotherapy to be successful, it must reverse these escape mechanisms, which necessitates explicit and tumor-specific elucidation of tumor escape strategies.
Research Design: To identify relevant escape mechanisms in murine tumors and in two corresponding human cancers, real-time reverse transcription-PCR was used to measure a panel of genes associated with T-cell activation and inhibition pathways.
Results: Comparative analysis of the expression levels of these immunomodulatory genes showed astonishing similarities in expression patterns between murine and human breast cancers but profound variability in the expression of immunomodulatory genes in colorectal cancers. For human ductal adenocarcinoma of the breast, down-regulation of dendritic cell maturation marker CD83 and T-cell activation gene CD28 was observed as well as a notable increase in the expression of the immunoinhibitory gene B7-H4. By contrast, colorectal adenocarcinoma cases showed high variability in tumor escape mechanisms, indicating a need to produce immune signatures for individual patients to identify appropriate immunotherapeutic targets.
Conclusions: These results show that certain tumors, such as ductal carcinoma of the breast, show consistent immunologic abnormalities that can be used as targets for immunotherapy. These findings also show the importance and feasibility of determining the immune signatures of patients' tumors to select appropriate immunotherapeutic strategies. Ultimately, these results advocate for the determination of immune signatures as part of the customary repertoire of clinical diagnostics for cancer.
