瑞士日内瓦大学Christoph Scheiermann等研究人员合作发现，CD8+T细胞的昼夜节律肿瘤浸润和功能决定免疫疗法的疗效。相关论文于2024年5月8日在线发表在《细胞》杂志上。
研究人员表示，肿瘤浸润淋巴细胞（尤其是CD8+ T细胞）的质量和数量是控制肿瘤生长和免疫疗法反应的重要参数。
研究人员在小鼠和人类癌症中发现，这些参数表现出昼夜节律振荡，其驱动因素包括白细胞的内源性昼夜节律时钟和白细胞的节律性浸润，而后者取决于肿瘤微环境中内皮细胞的昼夜节律时钟。为了在治疗上利用这些节律，研究人员证明了嵌合抗原受体T细胞疗法和免疫检查点阻断疗法的疗效可以通过调整白天的治疗时间来提高。此外，在小鼠肿瘤模型中，依赖于白天时间的T细胞特征可以预测黑色素瘤患者的总生存期，并与抗PD-1疗法的反应相关。这些数据证明了肿瘤微环境中昼夜节律动态的功能意义，并表明利用这些特征改善未来临床试验设计和患者护理的重要性。
附：英文原文
Title: Circadian tumor infiltration and function of CD8+ T cells dictate immunotherapy efficacy
Author: Chen Wang, Qun Zeng, Zeynep Melis Gül, Sisi Wang, Robert Pick, Phil Cheng, Ruben Bill, Yan Wu, Stefan Naulaerts, Coline Barnoud, Pei-Chun Hsueh, Sofie Hedlund Moller, Mara Cenerenti, Mengzhu Sun, Ziyang Su, Stéphane Jemelin, Volodymyr Petrenko, Charna Dibner, Stéphanie Hugues, Camilla Jandus, Zhongwu Li, Olivier Michielin, Ping-Chih Ho, Abhishek D. Garg, Federico Simonetta, Mikal J. Pittet, Christoph Scheiermann
Issue&Volume: 2024-05-08
Abstract: The quality and quantity of tumor-infiltrating lymphocytes, particularly CD8+ T cells, are important parameters for the control of tumor growth and response to immunotherapy. Here, we show in murine and human cancers that these parameters exhibit circadian oscillations, driven by both the endogenous circadian clock of leukocytes and rhythmic leukocyte infiltration, which depends on the circadian clock of endothelial cells in the tumor microenvironment. To harness these rhythms therapeutically, we demonstrate that efficacy of chimeric antigen receptor T cell therapy and immune checkpoint blockade can be improved by adjusting the time of treatment during the day. Furthermore, time-of-day-dependent T cell signatures in murine tumor models predict overall survival in patients with melanoma and correlate with response to anti-PD-1 therapy. Our data demonstrate the functional significance of circadian dynamics in the tumor microenvironment and suggest the importance of leveraging these features for improving future clinical trial design and patient care.
DOI: 10.1016/j.cell.2024.04.015
Source: https://www.cell.com/cell/fulltext/S0092-8674(24)00410-0