生物谷：美國(guó)Southern California大學(xué)的科學(xué)家最近表示，腫瘤最基本特征之一：如何躲避免疫系統(tǒng)攻擊將成為癌細(xì)胞最大弱點(diǎn),。研究小組針對(duì)乳腺癌和直腸癌的研究證實(shí),，一種尋找癌癥“免疫簽名”的技術(shù)能有助于某些特定癌癥的診斷和治療。
在7月1日的《臨床癌癥研究》（Clinical Cancer Research）上,，科學(xué)家描述了使用一種新技術(shù)來分析癌細(xì)胞中的基因變異,，這使得它們可以躲避身體免疫系統(tǒng)的防御?？茖W(xué)家相信這一技術(shù)將成為癌癥診斷和治療的標(biāo)準(zhǔn)手段之一,。
腫瘤細(xì)胞擁有多種基因和生物學(xué)變異。不同癌癥之間這種差異非常明顯,，即使在同種癌癥中也存在類似差別,。但是盡管組成免疫簽名的基因變異非常復(fù)雜，科學(xué)家還是發(fā)現(xiàn)了一小組基因在表達(dá)免疫學(xué)行為方面是完整的,。
利用一種實(shí)時(shí)高速基因放大技術(shù)PCR,，小組全面掃描了腫瘤，結(jié)果確認(rèn)了腫瘤中14個(gè)促進(jìn)免疫的基因和11個(gè)關(guān)鍵的對(duì)抗免疫的基因,。小組還分析了老鼠中乳腺癌,、白血病、腸癌,、肺癌和腎癌中這些基因的表達(dá),。他們比較了其中2種免疫簽名和相應(yīng)的人類腫瘤的差異。
結(jié)果發(fā)現(xiàn),，人類乳腺癌的免疫簽名和老鼠的符合得相當(dāng)好,。在所有病例中，科學(xué)家都發(fā)現(xiàn)了基因CD83和CD28被抑制,，這是兩個(gè)影響免疫細(xì)胞活性的基因,。而基因B7-H4得到促進(jìn)，它產(chǎn)生的蛋白能抑制免疫活性,。而腸癌的免疫簽名則有所變化,，這意味著需要對(duì)每個(gè)病人進(jìn)行分析。 （教育部科技發(fā)展中心)
原文鏈接：http://www.physorg.com/news102610745.html
原始出處:
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: [email protected] .
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.
