The Sidney Kimmel Cancer Center, Skip Viragh Clinical Pancreatic Cancer Center, Aurora, CO, USA.
Cancer J. 2012 Nov-Dec;18(6):642-52. doi: 10.1097/PPO.0b013e3182756903.
Pancreatic ductal adenocarcinoma (PDA) remains a highly lethal disease; new therapeutic modalities are urgently needed. A number of immunotherapies tested in preclinical models have shown promise. Early-phase clinical trials have demonstrated evidence of immune activation that in some cases correlates with clinical response. Moreover, recent evidence delineates the intricate role of inflammation in PDA, even at its earliest stages. Pancreatic ductal adenocarcinoma is thus ripe for immunotherapy; however, significant challenges remain before success can be realized. Future studies will need to focus on the discovery of novel PDA antigens and the identification of the multiple immune suppressive pathways within the PDA tumor microenvironment that inhibit an effective PDA-targeted immune response. Technologies are now available to rapidly advance discovery. Rapid translation of new discoveries into scientifically driven clinical trials testing combinations of immune agents will likely continue to shift the procarcinogenic tumor environment toward the most potent anticancer response.
胰腺导管腺癌 (PDA) 仍然是一种高度致命的疾病;迫切需要新的治疗方法。许多在临床前模型中测试的免疫疗法显示出了希望。早期临床试验已经证明了免疫激活的证据,在某些情况下,这种激活与临床反应相关。此外,最近的证据描绘了炎症在 PDA 中的复杂作用,即使在其最早阶段也是如此。因此,PDA 适合免疫治疗;然而,在取得成功之前,仍然存在重大挑战。未来的研究将需要专注于发现新的 PDA 抗原,以及确定 PDA 肿瘤微环境中抑制有效的 PDA 靶向免疫反应的多个免疫抑制途径。现在有技术可以快速推进发现。将新发现迅速转化为科学驱动的临床试验,测试免疫制剂的组合,可能会继续将致癌肿瘤环境推向最有效的抗癌反应。