Olin Michael R, Pluhar G Elizabeth, Andersen Brian M, Shaver Rob, Waldron Nate N, Moertel Christopher L
Department of Pediatrics. University of Minnesota, Minneapolis, MN 55445.
Department of Veterinary Medicine, College of Veterinary Medicine. University of Minnesota, St. Paul, MN 55108.
Crit Rev Immunol. 2014;34(5):399-432. doi: 10.1615/critrevimmunol.2014011577.
Anti-tumor immunotherapy using tumor lysate-based vaccines has made great advances over recent decades. Cancer vaccines aim to elicit adaptive immune responses through various pathways by providing tumor and tumor-associated antigens with an immune stimulant or adjuvant. These anti-tumor vaccines are therefore developed as personalized treatments. Utilizing tumors as a source of vaccine antigens in immunotherapy has demonstrated promising results with minimal toxicity. However, to date, researchers have failed to overcome the overpowering immune suppressive effects within the tumor microenvironment. Immune suppression occurs naturally via multiple mechanisms. These mechanisms serve an important homeostatic role restoring a normal tissue microenvironment following an inflammatory response. Due to these suppressive mechanisms and the inherent heterogeneity of tumors, it is imperative to then elicit and maintain a specific tumoricidal response if vaccine therapy or some other combination of reagents is chosen. In this review, we focus on the historical use of tumors as a source of antigens to elicit a tumoricidal response and the limitations encountered that prevent greater success in immunotherapy. We describe the advantages and disadvantages of various vaccines and their ineffectiveness due to tumor-induced immune suppression.
近几十年来,使用基于肿瘤裂解物的疫苗进行抗肿瘤免疫治疗取得了巨大进展。癌症疫苗旨在通过为肿瘤和肿瘤相关抗原提供免疫刺激剂或佐剂,通过各种途径引发适应性免疫反应。因此,这些抗肿瘤疫苗被开发为个性化治疗方法。在免疫治疗中利用肿瘤作为疫苗抗原的来源已显示出有希望的结果,且毒性最小。然而,迄今为止,研究人员尚未克服肿瘤微环境中压倒性的免疫抑制作用。免疫抑制通过多种机制自然发生。这些机制在炎症反应后恢复正常组织微环境方面起着重要的稳态作用。由于这些抑制机制以及肿瘤固有的异质性,如果选择疫苗治疗或其他某种试剂组合,那么引发并维持特定的杀肿瘤反应就势在必行。在这篇综述中,我们重点关注将肿瘤作为抗原来源以引发杀肿瘤反应的历史应用以及所遇到的限制,这些限制阻碍了免疫治疗取得更大成功。我们描述了各种疫苗的优缺点以及由于肿瘤诱导的免疫抑制导致的疫苗无效性。