研究癌細胞如何逃避免疫系統攻擊的研究人員發現：某些腫瘤的環加氧酶2(cyclooxygenase-2, COX-2)基因過度表達，防止樹突狀細胞參與Th1炎性反應并導致它們轉換進入Tr1免疫抑制模式。

在正常情況下，樹突狀細胞誘導生成白介素12(interleukin-12, IL-12)，IL12促使CD4+T淋巴細胞啟動T輔助細胞1(T help1, Th1)型炎癥反應。但是，在2004年10月1日出版的《免疫學期刊》(the Journal of Immunology)的一篇文章中， Cedars-Sinai醫學中心(Los Angeles, CA, USA; www.cedars-sinai.edu/mdnsi) Maxine Dunitz神經外科研究所的研究人員報道說：COX-2過度表達可以調節樹突狀細胞的生物學行為。

當樹突狀細胞暴露于癌細胞的時候，由于癌細胞過度表達COX-2導致前列腺素E2水平升高，樹突狀細胞促使白介素10以及轉化生長因子beta過度生成，而不是正常的白介素12生成。這兩種物質觸發Tr1調節反應，導致淋巴細胞對腫瘤抗原發生耐受。

Maxine Dunitz神經外科研究所《綜合腦組織腫瘤項目》合作主任、高級作者John S. Yu博士說：“腫瘤組織通過表達COX-2從而使它們逃避免疫系統的識別。通過使用COX-2抑制劑，可以使這些腫瘤容易被免疫系統發現，從而利于免疫系統摧毀這些腫瘤。這些令人振奮的發現之一是：從一例神經膠質母細胞瘤患者血流中分離出的T輔助細胞，對該患者的神經膠質瘤細胞產生明顯的調節反應。這點提示了在 惡性神經膠質瘤患者的循環T細胞中存在調節偏差。

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."