Wang et al. show that immune cell infiltration of tumours, as well as immune cell phenotype, oscillate in a circadian manner, which can be harnessed to optimize cancer immunotherapy. In a mouse model of melanoma, the numbers of tumour infiltrating leukocytes (TILs) peaked in the evening, and this was due to fluctuating levels of the adhesion molecule ICAM-1 on endothelial cells. Treatment with chimeric antigen receptor (CAR) T cells in the evening, as compared to the morning, induced greater tumour shrinkage. Moreover, surface expression of the checkpoint molecule PD1 on CD8⁺ T cells peaked in the evening, and in mouse models of melanoma and colon carcinoma, treatment with PD1-targeted antibodies showed an effect in the evening but not in the morning. Similar time-of-day differences in TIL number and phenotype were found in humans with melanoma, albeit phase-shifted, as expected for diurnal humans versus nocturnal mice. The implications of these results with regards to timing of immunotherapy will need to be tested in future clinical trials.

王等人。研究表明，肿瘤的免疫细胞浸润以及免疫细胞表型以昼夜节律方式振荡，这可以用来优化癌症免疫治疗。在黑色素瘤小鼠模型中，肿瘤浸润白细胞 (TIL) 的数量在晚上达到峰值，这是由于内皮细胞上粘附分子 ICAM-1 水平的波动造成的。与早上相比，晚上使用嵌合抗原受体 (CAR) T 细胞治疗可诱导更大的肿瘤缩小。此外，CD8 ⁺ T细胞上检查点分子PD1的表面表达在晚上达到峰值，在黑色素瘤和结肠癌的小鼠模型中，PD1靶向抗体的治疗在晚上显示出效果，但在早上则没有效果。在患有黑色素瘤的人类中也发现了类似的 TIL 数量和表型的不同时间差异，尽管存在相移，正如白天人类与夜间小鼠的预期一样。这些结果对免疫治疗时机的影响需要在未来的临床试验中进行测试。