Current progress in immunotherapy for pancreatic cancer.
Current progress in immunotherapy for pancreatic cancer.
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DOI：
10.1016/j.canlet.2015.12.020
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发表时间：
2016-10-10
期刊：
影响因子：
9.7
通讯作者：
Zheng L
中科院分区：
文献类型：
--
作者：
Foley K;Kim V;Jaffee E;Zheng L
胰腺癌仍然是最致命的癌症之一，治疗选择很少。基于免疫的治疗胰腺癌的策略，如免疫检查点抑制剂，治疗性疫苗和联合免疫疗法，在其他方法失败的情况下显示出希望。免疫检查点抑制剂，包括抗CTLA 4、抗PD-1和抗PD-L1抗体，作为单一药物在免疫敏感性癌症如黑色素瘤中是有效的，但在免疫不敏感性癌症包括胰腺癌中缺乏疗效。然而，这些抑制剂显示出临床活性，即使在传统的非免疫原性癌症中，当与其他干预措施，包括化疗，放疗和治疗性疫苗组合时。与免疫调节剂一起给予的治疗性疫苗特别令人感兴趣，因为疫苗是诱导有效的抗肿瘤T细胞应答的最有效方式，这是免疫疗法有效所需的。在胰腺癌中，早期研究表明疫苗可以诱导具有识别和杀死胰腺癌细胞潜力的T细胞，但肿瘤微环境抑制了有效的T细胞运输和功能。虽然在过去几年中，胰腺癌免疫疗法的发展取得了进展，但还需要进行更多的试验，以更好地了解肿瘤微环境中的信号，这些信号是T细胞浸润和功能的强大障碍。此外，随着越来越多的胰腺特异性抗原被鉴定出来，免疫疗法将继续得到改进，以提供最显著的临床益处。
Pancreatic cancer remains one of the most lethal cancers with few treatment options. Immune-based strategies to treat pancreatic cancer, such as immune checkpoint inhibitors, therapeutic vaccines, and combination immunotherapies, are showing promise where other approaches have failed. Immune checkpoint inhibitors, including anti-CTLA4, anti-PD-1, and anti-PD-L1 antibodies, are effective as single agents in immune sensitive cancers like melanoma, but lack efficacy in immune insensitive cancers including pancreatic cancer. However, these inhibitors are showing clinical activity, even in traditionally non-immunogenic cancers, when combined with other interventions, including chemotherapy, radiation therapy, and therapeutic vaccines. Therapeutic vaccines given together with immune modulating agents are of particular interest because vaccines are the most efficient way to induce effective anti-tumor T cell responses, which is required for immunotherapies to be effective. In pancreatic cancer, early studies suggest that vaccines can induce T cells that have the potential to recognize and kill pancreatic cancer cells, but the tumor microenvironment inhibits effective T cell trafficking and function. While progress has been made in the development of immunotherapies for pancreatic cancer over the last several years, additional trials are needed to better understand the signals within the tumor microenvironment that are formidable barriers to T cell infiltration and function. Additionally, as more pancreatic specific antigens are identified, immunotherapies will continue to be refined to provide the most significant clinical benefit.