Chronotherapy with immune checkpoint inhibitors: The knowns, the unknowns, and the contested.

Immune checkpoint inhibitors show time-of-day-dependent effects in pre-clinical models and earlier treatment timing is linked to better outcomes in retrospective trials.

• Why it matters: Understanding the reproducibility and mechanisms of these effects is crucial for optimizing immunotherapy timing and improving patient outcomes, yet key questions remain unresolved.
• What they did: The authors review emerging pre-clinical data and retrospective clinical trial associations, discussing open questions about reproducibility, underlying biological mechanisms, and clinical implications.
• The result: Clarifying these issues may enable the development of chronotherapy strategies that enhance the efficacy of immune checkpoint inhibitors in cancer treatment.