COX-2帮助癌细胞逃避免疫系统的攻击

研究癌细胞如何逃避免疫系统攻击的研究人员发现：某些肿瘤的环加氧酶2(cyclooxygenase-2, COX-2)基因过度表达，防止树突状细胞参与Th1炎性反应并导致它们转换进入Tr1免疫抑制模式。

在正常情况下，树突状细胞诱导生成白介素12(interleukin-12, IL-12)，IL12促使CD4+T淋巴细胞启动T辅助细胞1(T help1, Th1)型炎症反应。但是，在2004年10月1日出版的《免疫学期刊》(the Journal of Immunology)的一篇文章中， Cedars-Sinai医学中心(Los Angeles, CA, USA; www.cedars-sinai.edu/mdnsi) Maxine Dunitz神经外科研究所的研究人员报道说：COX-2过度表达可以调节树突状细胞的生物学行为。

当树突状细胞暴露于癌细胞的时候，由于癌细胞过度表达COX-2导致前列腺素E2水平升高，树突状细胞促使白介素10以及转化生长因子beta过度生成，而不是正常的白介素12生成。这两种物质触发Tr1调节反应，导致淋巴细胞对肿瘤抗原发生耐受。

Maxine Dunitz神经外科研究所《综合脑组织肿瘤项目》合作主任、高级作者John S. Yu博士说：“肿瘤组织通过表达COX-2从而使它们逃避免疫系统的识别。通过使用COX-2抑制剂，可以使这些肿瘤容易被免疫系统发现，从而利于免疫系统摧毁这些肿瘤。这些令人振奋的发现之一是：从一例神经胶质母细胞瘤患者血流中分离出的T辅助细胞，对该患者的神经胶质瘤细胞产生明显的调节反应。这点提示了在 恶性神经胶质瘤患者的循环T细胞中存在调节偏差。

COX-2 Helps Cancer Cells Avoid Immune Attack
 
Researchers studying how cancer cells avoid attack by the immune system have found that overexpression of the gene for cyclooxygenase-2 (COX-2) by certain tumors prevents dendritic cells from staging a Th1 inflammatory response and causes them to shift into a Tr1 immunosuppressive mode.

Normally, dendritic cells induce the production of interleukin-12 (IL-12), which prompts CD4+ T lymphocytes to launch a T helper type 1 (Th1) inflammatory response. However, in the current study published in the October 1, 2004, issue of the Journal of Immunology, investigators at the Maxine Dunitz Neurosurgical Institute of Cedars-Sinai Medical Center (Los Angeles, CA, USA; www.cedars-sinai.edu/mdnsi) reported that overexpression of COX-2 modified dendritic cell behavior.

When dendritic cells were exposed to cancer cells whose COX-2 overexpression caused elevated levels of prostaglandin E2, the dendritic cells prompted the overproduction of interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta) instead of inducing the production of interleukin-12 (IL-12). These two substances triggered a Trl regulatory response that caused lymphocytes to be tolerant of tumor cell antigens.

Senior author Dr. John S. Yu, co-director of the comprehensive brain tumor program at the Maxine Dunitz Neurosugical Institute, said, “COX-2 expression by tumors may make them invisible to the immune system. By using COX-2 inhibitors, these tumors may become more detectable and therefore more vulnerable to destruction by the immune system. One of the intriguing findings was that helper cells isolated from the bloodstream of a glioblastoma patient predominantly displayed a regulatory response against the patient’s glioma cells. This points to the existence of an underlying regulatory bias in the circulating T cells of patients with malignant glioma."