Foley Kelly, Kim Victoria, Jaffee Elizabeth, Zheng Lei
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, United States; The Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, United States; The Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Cancer Lett. 2016 Oct 10;381(1):244-51. doi: 10.1016/j.canlet.2015.12.020. Epub 2015 Dec 23.
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.
胰腺癌仍然是致死率最高的癌症之一,治疗选择有限。基于免疫的胰腺癌治疗策略,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了前景。免疫检查点抑制剂,包括抗CTLA4、抗PD-1和抗PD-L1抗体,在黑色素瘤等免疫敏感癌症中作为单一药物有效,但在包括胰腺癌在内的免疫不敏感癌症中缺乏疗效。然而,当与包括化疗、放疗和治疗性疫苗在内的其他干预措施联合使用时,这些抑制剂即使在传统上非免疫原性的癌症中也显示出临床活性。与免疫调节剂一起使用的治疗性疫苗尤其令人感兴趣,因为疫苗是诱导有效的抗肿瘤T细胞反应的最有效方法,而这是免疫疗法有效所必需的。在胰腺癌中,早期研究表明疫苗可以诱导有可能识别并杀死胰腺癌细胞的T细胞,但肿瘤微环境会抑制有效的T细胞运输和功能。尽管在过去几年中胰腺癌免疫疗法的开发取得了进展,但仍需要更多试验来更好地了解肿瘤微环境中对T细胞浸润和功能构成巨大障碍的信号。此外,随着更多胰腺特异性抗原被识别,免疫疗法将继续得到改进,以提供最显著的临床益处。