, Newtown, USA.
Curr Oncol Rep. 2018 Feb 7;20(1):8. doi: 10.1007/s11912-018-0662-5.
In 2016, the American Society of Clinical Oncology (ASCO) announced immunotherapy as the year's top cancer advance in its "Clinical Cancer Advances 2016: ASCO's Annual Report on Progress Against Cancer." Further, ASCO again named "Immunotherapy 2.0" as the 2017 advance of the year, emphasizing the recent, rapid pace of research into new agents that harness and enhance the innate abilities of the immune system to recognize and fight cancers-and stressing that such agents have extended the lives of many patients with late-stage cancers for which there have been few treatment options. This article discusses the history of cancer immunotherapy and the recent promising advances, yet also presents a note of caution on limitations of immunotherapies, their potential harms, and the critical need for oncologists to appropriately engage with and educate patients to effectively manage their expectations.
Learning how to effectively harness the immune system to treat cancer represents an investigative journey of more than 100 years. However, after many failures and disappointments, this decade has seen several important successes. In 2011, the Food and Drug Administration (FDA) approved the first immunotherapy agent known as a "checkpoint inhibitor." Beginning in 2014, several additional checkpoint blockage drugs have been FDA-approved, and new indications and drug combinations have emerged. Further, on August 30, 2017, the FDA announced its first approval of a new form of immunotherapy known as CAR T cell therapy. Since the 2011 approval of the first checkpoint inhibitor, cancer immunotherapy research among the pharmaceutical industry and research institutions has exploded, with thousands of clinical trials currently taking place. The current "cancer immunotherapy revolution" is in the headlines daily and is also the primary topic of conversation among major cancer research conferences and symposia attendees. However, a once quiet voice has begun to emerge, where an increasing number of scientists, clinicians, and patient advocates are stressing the need for caution concerning the limitations and potential harms associated with cancer immunotherapy. Many oncologists, scientists, medical professional associations, and advocates agree that no recent cancer advance has been as successful, transformative, and potentially paradigm-shifting as immunotherapy. With this decade, we have seen the approval of several immunotherapy agents that have successfully treated a percentage of patients with notoriously resistant cancers, an increasing number of combination immunotherapy treatments, and new indications for approved agents. However, patients need to be aware that much of the popular media has breathlessly inflated positive outcomes of cancer immunotherapies, while neglecting to stress that just a small percentage of patients actually benefit from such treatments. Further, they often completely overlook the unique, potentially life-threatening harms that may be associated with these agents and fail to cover negative findings where immunotherapies have appeared to paradoxically accelerate cancer growth. Fortunately, the majority of journal articles presenting trial results and comprehensive review articles appropriately discuss the important limitations associated with immunotherapies, the unique spectrum of adverse effects, and the need for further research to improve our ability to identify those patients who are most likely to benefit from specific agents, sparing other patients from exposure to agents that will not be effective, yet may carry potentially life-threatening toxicities.
2016 年，美国临床肿瘤学会（ASCO）在其“2016 年临床癌症进展：ASCO 癌症进展年度报告”中宣布免疫疗法为当年癌症领域的重大进展。此外，ASCO 再次将“免疫疗法 2.0”评为 2017 年的进展，强调了最近新药物研究的快速发展，这些新药物利用和增强了免疫系统识别和对抗癌症的固有能力，并强调这些药物延长了许多晚期癌症患者的生命，而这些患者的治疗选择很少。本文讨论了癌症免疫疗法的历史和最近有希望的进展，但也对免疫疗法的局限性、潜在危害提出了警告，并强调肿瘤学家有必要与患者进行适当的接触和教育，以有效管理他们的期望。
有效利用免疫系统治疗癌症是一项超过 100 年的探索性研究。然而，在经历了许多失败和失望之后，这十年取得了一些重要的成功。2011 年，美国食品和药物管理局（FDA）批准了第一种被称为“检查点抑制剂”的免疫治疗药物。从 2014 年开始，又有几种检查点阻断药物获得了 FDA 的批准，并且出现了新的适应症和药物组合。此外，2017 年 8 月 30 日，FDA 宣布批准了一种新形式的免疫疗法，即嵌合抗原受体 T 细胞疗法。自 2011 年第一种检查点抑制剂获得批准以来，制药行业和研究机构的癌症免疫疗法研究如雨后春笋般涌现，目前正在进行数千项临床试验。当前的“癌症免疫疗法革命”每天都在头条新闻中出现，也是各大癌症研究会议和研讨会与会者的主要话题。然而，一个曾经悄无声息的声音开始出现，越来越多的科学家、临床医生和患者倡导者强调，需要谨慎对待与癌症免疫疗法相关的局限性和潜在危害。许多肿瘤学家、科学家、医学专业协会和倡导者都认为，没有最近的癌症进展像免疫疗法那样成功、具有变革性和潜在的范式转变。在这十年中，我们已经看到了几种免疫治疗药物的批准，这些药物成功地治疗了一些对恶性肿瘤具有明显耐药性的患者，越来越多的免疫联合治疗方法，以及已批准药物的新适应症。然而，患者需要意识到，许多大众媒体都在大肆宣扬癌症免疫疗法的积极结果，而忽略了强调只有一小部分患者实际上从这些治疗中受益。此外，他们经常完全忽略了这些药物可能带来的独特的、潜在的危及生命的危害，并且未能报道免疫疗法似乎反而加速癌症生长的负面发现。幸运的是，大多数发表试验结果的期刊文章和全面的综述文章都适当地讨论了与免疫疗法相关的重要局限性、独特的不良反应谱，以及进一步研究以提高我们识别最有可能从特定药物中获益的患者的能力的必要性，使其他患者免受可能无效但可能具有潜在生命威胁毒性的药物的暴露。
