Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
Biomedical Engineering, Bucknell University, Lewisburg, PA, 17837, USA.
Adv Sci (Weinh). 2023 Dec;10(36):e2304076. doi: 10.1002/advs.202304076. Epub 2023 Nov 10.
Effective anti-cancer immune responses require activation of one or more naïve T cells. If the correct naïve T cell encounters its cognate antigen presented by an antigen presenting cell, then the T cell can activate and proliferate. Here, mathematical modeling is used to explore the possibility that immune activation in lymph nodes is a rate-limiting step in anti-cancer immunity and can affect response rates to immune checkpoint therapy. The model provides a mechanistic framework for optimizing cancer immunotherapy and developing testable solutions to unleash anti-tumor immune responses for more patients with cancer. The results show that antigen production rate and trafficking of naïve T cells into the lymph nodes are key parameters and that treatments designed to enhance tumor antigen production can improve immune checkpoint therapies. The model underscores the potential of radiation therapy in augmenting tumor immunogenicity and neoantigen production for improved ICB therapy, while emphasizing the need for careful consideration in cases where antigen levels are already sufficient to avoid compromising the immune response.
有效的抗癌免疫反应需要激活一个或多个幼稚 T 细胞。如果正确的幼稚 T 细胞遇到其同源抗原被抗原呈递细胞呈递，那么 T 细胞可以激活和增殖。在这里，数学建模被用来探索淋巴结中的免疫激活是否是抗癌免疫的限速步骤，并可能影响免疫检查点治疗的反应率。该模型为优化癌症免疫疗法提供了一个机制框架，并为释放抗肿瘤免疫反应以造福更多癌症患者开发了可测试的解决方案。结果表明，抗原产生率和幼稚 T 细胞向淋巴结的运输是关键参数，旨在增强肿瘤抗原产生的治疗方法可以改善免疫检查点治疗。该模型强调了放射治疗在增强肿瘤免疫原性和新抗原产生以改善 ICB 治疗方面的潜力，同时强调在抗原水平已经足够的情况下需要谨慎考虑，以避免损害免疫反应。
