Plate Janet M D
Department of Medicine, Division of Oncology, Hematology and Stem Cell Transplantation, Rush University Medical Center, 1653 W. Congress Parkway, Chicago, Illinois 60612, USA.
Discov Med. 2012 Aug;14(75):89-94.
Pancreatic cancer is one of the most difficult-to-treat cancers. Despite surgical resection, radiation and/or chemotherapy, greater than 94% of people with pancreatic cancer do not survive beyond 5 years. In fact, median survival after diagnosis of metastatic pancreatic cancer is 4.5 months. The majority of patients are diagnosed with nonresectable, metastatic disease, and chemotherapy only extends their median survival by less than 2 months with only 18% of those treated surviving beyond 1 year. Despite the severity of their disease, most patients exhibit tumor specific cellular immunity to their pancreatic cancer antigens. Obviously their immunity is ineffective in preventing tumor growth. Recent studies have demonstrated that the tumor microenvironment may hold the key to determining the nature of the tumors' ability to escape from immune attack. Preliminary clinical trials have suggested that blocking these escape mechanisms may result in survival benefit to the patients, and phase I and II clinical trials with tumor vaccines have led to some survival benefits. Perhaps combining therapies directed against immune escape mechanisms with tumor vaccines will result in even greater survival benefit for patients with pancreatic cancer. While therapeutic vaccines for pancreatic cancers have been reviewed previously (Plate, 2011), updates on recent preliminary reports of two clinical vaccine trials are worthy of our attention.
胰腺癌是最难治疗的癌症之一。尽管进行了手术切除、放疗和/或化疗,但超过94%的胰腺癌患者生存期不超过5年。事实上,转移性胰腺癌确诊后的中位生存期为4.5个月。大多数患者被诊断为不可切除的转移性疾病,化疗仅将他们的中位生存期延长不到2个月,接受治疗的患者中只有18%能存活超过1年。尽管病情严重,但大多数患者对其胰腺癌抗原表现出肿瘤特异性细胞免疫。显然,他们的免疫在预防肿瘤生长方面无效。最近的研究表明,肿瘤微环境可能是决定肿瘤逃避免疫攻击能力本质的关键。初步临床试验表明,阻断这些逃逸机制可能会给患者带来生存益处,肿瘤疫苗的I期和II期临床试验已带来了一些生存益处。也许将针对免疫逃逸机制的疗法与肿瘤疫苗相结合,将给胰腺癌患者带来更大的生存益处。虽然之前已经对胰腺癌的治疗性疫苗进行了综述(普拉特,2011年),但两项临床疫苗试验近期初步报告的更新值得我们关注。