Section of Upper Abdominal Surgery at Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Surgery, The Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden; Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, Stockholm, Sweden.
Chin Clin Oncol. 2022 Feb;11(1):4. doi: 10.21037/cco-21-174.
Immunotherapy is the fastest growing branch in oncology that have already revolutionized the treatment of few solid cancers. The number of immunotherapy trials for pancreatic cancer (PC) is growing but the vast number of different agents used make it difficult to comprehend a possible success trait of a certain type of immunotherapy. The aim of this review is to summarize and critically evaluate the outcome of immunotherapy trials for PC intended to aid the comprehensiveness for the treating physicians.
A PubMed search was performed to identify clinical trials in patients with PC, published in English from year 2000 to June 2021 and using combination of the terms immunotherapy, PC, and cross-checked the bibliography of the revised literature as the dublettes have been removed. Studies were divided into three groups depending on what immune components have been applied: passive products (peptides, antibodies, etc.), antigen-presenting cells, and adoptive cell transfer trials.
The vast majority of trials, including those from most recent years, used passive products of the immune system-peptide vaccines and antibodies. The administration was often parallel to chemotherapy that was prevalently gemcitabine-based. Although immunological responses have been detected, the clinical efficacy was very limited. Trials with check point inhibitors did not show survival advantage. Dendritic cell (DC) vaccines have been associated with some clinical objective response and prolonged survival in few patients with delayed type hypersensitivity reactions. Trials with adoptive transfer therapy are lacking. The very few trials with lymphokine-activated killer (LAK)/cytokine-induced killer (CIK) cells tested only in Asian population have resulted in some clinical effects with prolonged survival. In none of the trials have the patients been preconditioned before receiving immunotherapy.
Although the clinical effectiveness in the majority of the reported trials has been limited, the immunological effects observed in almost all trials show a proof of concept-that immunotherapy can work. Careful re-evaluation of the clinical premises and focus on combination and cell therapy may be the way to achieve improved survival by immunotherapy in PC.
免疫疗法是肿瘤学发展最快的分支,它已经彻底改变了几种实体癌症的治疗方法。用于胰腺癌(PC)的免疫疗法试验数量正在增加,但使用的大量不同药物使得很难理解某种免疫疗法的可能成功特征。本综述的目的是总结和批判性评估旨在帮助治疗医生全面了解的用于 PC 的免疫疗法试验的结果。
在 PubMed 上进行了搜索,以确定 2000 年至 2021 年 6 月期间以英文发表的用于 PC 患者的临床试验,并使用免疫疗法、PC 和交叉检查修订文献的参考文献作为重复项已被删除。研究根据应用的免疫成分分为三组:被动产品(肽、抗体等)、抗原呈递细胞和过继细胞转移试验。
绝大多数试验,包括最近几年的试验,都使用了免疫系统的被动产品-肽疫苗和抗体。给药通常与以吉西他滨为基础的化疗同时进行。尽管已经检测到免疫反应,但临床疗效非常有限。检查点抑制剂的试验未显示生存优势。树突状细胞(DC)疫苗与少数患者的迟发型超敏反应相关联,这些患者具有一些临床客观反应和延长的生存时间。过继转移治疗试验缺乏。在仅在亚洲人群中测试的少数淋巴因子激活的杀伤(LAK)/细胞因子诱导的杀伤(CIK)细胞试验中,一些临床试验结果和延长的生存时间。在没有一项试验中,患者在接受免疫疗法之前进行了预处理。
尽管报告的大多数试验的临床效果有限,但几乎所有试验中观察到的免疫效应都证明了一个概念,即免疫疗法是有效的。仔细重新评估临床前提并专注于联合和细胞疗法,可能是通过免疫疗法改善 PC 患者生存的方法。