免疫疗法与传统治疗标准相结合，如化疗、放疗和手术，是癌症患者 的附加支柱。它彻底改变了癌症治疗，并使肿瘤免疫学领域焕发新生。多种类型的免疫疗法，包括养成细胞疗法（ACT）和检查点抑制剂（CPIs），都可以引起持久的临床反应。然而，它们的疗效各不相同，只有少数癌症患者从中受益。在本综述中，我们阐述三个目标：提供对这些方法的历史洞察，拓宽我们对免疫干预的理解，并讨论当前和未来的方法。我们重点介绍了癌症免疫疗法的演变，并讨论了如何通过个体化的免疫干预来解决现行的限制。癌症免疫疗法被认为是近年来的医学成就，并于2013年被《科学》评选为“科学突破年度大奖”。虽然免疫治疗的广度迅速扩展，包括使用嵌合抗原受体（CAR）T细胞疗法和免疫检查点抑制剂（ICI）疗法，但免疫疗法的历史可以追溯到3000年前。免疫疗法的广泛历史和相关观察结果，使得一些已批准的免疫治疗药物不仅限于近期的CAR-T和ICI疗法。除了其他经典的免疫干预方法，包括人乳头瘤病毒（HPV）、乙型肝炎和卡介苗结核疫苗的使用，免疫疗法对癌症治疗和预防产生了广泛持久的影响。免疫疗法的一个典型范例是1976年在患有膀胱癌的患者中使用卡介苗疗法，产生了70%的消除率，并已成为标准疗法。然而，免疫疗法的更大影响是通过预防致癌HPV感染，该感染负责98%的宫颈癌病例。2020年，世界卫生组织（WHO）估计有341,831名妇女死于宫颈癌。然而，单剂次双价HPV疫苗的接种被证明可以97.5%有效地预防HPV感染。这些疫苗不仅可以预防宫颈鳞状细胞癌和腺癌，还可以预防口腔睾丸、肛门、外阴、阴道和阴茎鳞状细胞癌。这些疫苗的广度、反应和持久性可以与CAR-T细胞疗法进行对比，其在广泛应用中存在诸多障碍，包括后勤、制造限制、毒性问题、财务负担和仅有30%至40%的反应患者产生持久缓解。另外，ICIs是另一个近期的免疫疗法焦点。ICIs是一类抗体，可以增强患者的免疫反应对抗癌细胞。然而，ICIs只对具有高突变负担的肿瘤有效，并伴有广谱毒性，需要中断给药和/或皮质类固醇的治疗，二者都限制了免疫治疗。总之，免疫治疗有着广泛的全球影响，利用了众多的行动机制，并在总体上对更广泛范围的肿瘤比最初考虑的要更有效。当多种免疫干预机制与标准治疗方法相结合时，这些新型癌症干预方法具有巨大的潜力和重要性。版权所有© 2023 Elsevier B.V。

Immunotherapy is an additional pillar when combined with traditional standards of care such as chemotherapy, radiotherapy, and surgery for cancer patients. It has revolutionized cancer treatment and rejuvenated the field of tumor immunology. Several types of immunotherapies, including adoptive cellular therapy (ACT) and checkpoint inhibitors (CPIs), can induce durable clinical responses. However, their efficacies vary, and only subsets of cancer patients benefit from their use. In this review, we address three goals: to provide insight into the history of these approaches, broaden our understanding of immune interventions, and discuss current and future approaches. We highlight how cancer immunotherapy has evolved and discuss how personalization of immune intervention may address present limitations. Cancer immunotherapy is considered a recent medical achievement and in 2013 was selected as the "Breakthrough of the Year" by Science. While the breadth of immunotherapeutics has been rapidly expanding, to include the use of chimeric antigen receptor (CAR) T-cell therapy and immune checkpoint inhibitor (ICI) therapy, immunotherapy dates back over 3000 years. The expansive history of immunotherapy, and related observations, have resulted in several approved immune therapeutics beyond the recent emphasis on CAR-T and ICI therapies. In addition to other classical forms of immune intervention, including human papillomavirus (HPV), hepatitis B, and the Mycobacterium bovis Bacillus Calmette-Guérin (BCG) tuberculosis vaccines, immunotherapies have had a broad and durable impact on cancer therapy and prevention. One classic example of immunotherapy was identified in 1976 with the use of intravesical administration of BCG in patients with bladder cancer; resulting in a 70 % eradication rate and is now standard of care. However, a greater impact from the use of immunotherapy is documented by the prevention of HPV infections that are responsible for 98 % of cervical cancer cases. In 2020, the World Health Organization (WHO) estimated that 341,831 women died from cervical cancer [1]. However, administration of a single dose of a bivalent HPV vaccine was shown to be 97.5 % effective in preventing HPV infections. These vaccines not only prevent cervical squamous cell carcinoma and adenocarcinoma, but also oropharyngeal, anal, vulvar, vaginal, and penile squamous cell carcinomas. The breadth, response and durability of these vaccines can be contrasted with CAR-T-cell therapies, which have significant barriers to their widespread use including logistics, manufacturing limitations, toxicity concerns, financial burden and lasting remissions observed in only 30 to 40 % of responding patients. Another, recent immunotherapy focus are ICIs. ICIs are a class of antibodies that can increase the immune responses against cancer cells in patients. However, ICIs are only effective against tumors with a high mutational burden and are associated with a broad spectrum of toxicities requiring interruption of administration and/or administration corticosteroids; both of which limit immune therapy. In summary, immune therapeutics have a broad impact worldwide, utilizing numerous mechanisms of action and when considered in their totality are more effective against a broader range of tumors than initially considered. These new cancer interventions have tremendous potential notability when multiple mechanisms of immune intervention are combined as well as with standard of care modalities.Copyright © 2023 Elsevier B.V. All rights reserved.