Stanton Sasha E, Anderson Kristin G, Bruno Tullia C, Capitini Christian M, Disis Mary L, McQuade Jennifer, Radvanyi Laszlo, Vanpouille-Box Claire, Wargo Jennifer, Baines Kelly J, Hong Megan M Y, Rajeh Adnan, Kim Raymond H, Awadalla Phillip, Hughes Lauren K, Maleki Vareki Saman
Earle A Chiles Research Institute, Providence Cancer Institute, Portland, Oregon, USA
Department of Microbiology, Immunology and Cancer Biology, Department of Obstetrics and Gynecology, Beirne B. Carter Center for Immunology Research and the University of Virginia Comprehensive Cancer Center, University of Virginia, Charlottesville, Virginia, UK.
J Immunother Cancer. 2025 Mar 28;13(3):e010419. doi: 10.1136/jitc-2024-010419.
Cancer immunotherapy has improved the survival of a subset of patients by harnessing the power of the immune system to find and destroy malignant cells. The immune system also protects the host by destroying developing premalignant and malignant tumors. Advancing our knowledge of premalignant immunity and immune changes seen in lesions that develop into invasive cancer versus those that regress offers an exciting opportunity to leverage the immune system for immune prevention and immune interception of premalignancy. Understanding the immune environment of premalignant lesions and how chronic inflammation plays a central role in the evolution of premalignancy is essential for developing effective immunoprevention and immune interceptions. Factors such as host genomics and environmental factors that affect premalignant immunity and the outcome of advanced cancers are equally important in determining the response to immunotherapy. The broad use of antibiotics and factors such as obesity can disrupt a healthy gut microbiome and drive chronic inflammation that suppresses preventive immunity or the antitumor immune response required for successful immunotherapy in advanced cancers. Modifiable lifestyle factors such as diet, obesity, smoking, and stress should be considered in designing immune prevention and interception studies, as well as for patients who receive immunotherapy for advanced cancer treatment. Other factors, such as the overall immune health of patients and existing comorbidities, affect both premalignant immunity and response to immunotherapy and, therefore, should be considered in managing patients with or without cancer. The Society for Immunotherapy of Cancer previously developed an overarching manuscript regarding the challenges and opportunities that exist in cancer immunotherapy, and this manuscript serves as an in-depth follow-up regarding the topics of premalignant immunity, immune interception, and immunoprevention, and the impact of the host on responding to immunotherapy.
癌症免疫疗法通过利用免疫系统的力量来发现和摧毁恶性细胞，提高了一部分患者的生存率。免疫系统还通过摧毁正在形成的癌前病变和恶性肿瘤来保护宿主。深入了解癌前免疫以及在发展为浸润性癌的病变与消退的病变中所观察到的免疫变化，为利用免疫系统进行癌前病变的免疫预防和免疫拦截提供了一个令人兴奋的机会。了解癌前病变的免疫环境以及慢性炎症在癌前病变演变过程中如何发挥核心作用，对于开发有效的免疫预防和免疫拦截至关重要。宿主基因组学和环境因素等影响癌前免疫和晚期癌症结局的因素，在确定对免疫疗法的反应方面同样重要。抗生素的广泛使用以及肥胖等因素会破坏健康的肠道微生物群，并引发慢性炎症，从而抑制预防性免疫或晚期癌症成功免疫疗法所需的抗肿瘤免疫反应。在设计免疫预防和拦截研究时，以及对于接受晚期癌症免疫治疗的患者，应考虑饮食、肥胖、吸烟和压力等可改变的生活方式因素。其他因素，如患者的整体免疫健康状况和现有合并症，会影响癌前免疫和对免疫疗法的反应，因此，在管理患有或未患癌症的患者时都应予以考虑。癌症免疫治疗协会此前编写了一份关于癌症免疫治疗中存在的挑战和机遇的总体稿件，而本稿件则是关于癌前免疫、免疫拦截和免疫预防主题以及宿主对免疫治疗反应的影响的深入跟进。
