In the era of precision medicine, mounting evidence suggests that the time of therapy administration, or chronotherapy, has a great impact on treatment outcomes. Chronotherapy involves planning treatment timing by considering circadian rhythms, which are 24 h oscillations in behavior and physiology driven by synchronized molecular clocks throughout the body. The value of chronotherapy in cancer treatment is currently under investigation, notably in the effects of treatment timing on efficacy and side effects. Immune checkpoint inhibitor (ICI) therapy is a promising cancer treatment. However, many patients still experience disease progression or need to stop the therapy early due to side effects. There is accumulating evidence that the time of day at which ICI therapy is administered can have a substantial effect on ICI efficacy. Thus, it is important to investigate the intersections of circadian rhythms, chronotherapy, and ICI efficacy. In this review, we provide a brief overview of circadian rhythms in the context of immunity and cancer. Additionally, we outline current applications of chronotherapy for cancer treatment. We synthesize the 29 studies conducted to date that examine the impact of time-of-day administration on the efficacy of ICI therapy, its associated side effects, and sex differences in both efficacy and side effects. We also discuss potential mechanisms underlying these observed results. Finally, we highlight the challenges in this area and future directions for research, including the potential for a chronotherapeutic personalized medicine approach that tailors the time of ICI administration to individual patients’ circadian rhythms.
在精准医疗时代，越来越多的证据表明治疗给药时间（即时间疗法）对治疗效果具有重要影响。时间疗法通过考虑昼夜节律来规划治疗时机，这种节律是由全身同步分子钟驱动的行为与生理的24小时周期性振荡。目前时间疗法在癌症治疗中的价值正在被深入研究，特别是在治疗时机对疗效和副作用的影响方面。免疫检查点抑制剂（ICI）疗法是一种前景广阔的癌症治疗手段，但许多患者仍面临疾病进展或因副作用而需提前终止治疗的问题。越来越多的证据表明，ICI疗法的给药时间点会对其疗效产生显著影响。因此，研究昼夜节律、时间疗法与ICI疗效之间的交叉关系至关重要。本综述简要概述了免疫与癌症背景下的昼夜节律机制，梳理了时间疗法在癌症治疗中的当前应用。我们系统整合了迄今开展的29项研究，这些研究探讨了给药时间对ICI疗法疗效、相关副作用的影响，以及疗效与副作用中存在的性别差异。同时，我们讨论了这些观察结果背后的潜在机制。最后，我们指出了该领域面临的挑战及未来研究方向，包括开发基于时间疗法的个性化医疗方案——根据患者个体昼夜节律特征定制ICI给药时间。
肿瘤(癌症)患者之家