CELL INTELLIGENCE · 肿瘤细胞治疗研究

Sleep is a fundamental health-related behavior that plays a central role in physiological regulation, yet its longitudinal association with biological regulation and long-term health outcomes during intensive medical treatment remains poorly characterized. This prospective cohort study examined whether receipt of a structured sleep optimization program during immune checkpoint inhibitor therapy was associated with longitudinal changes in sleep quality, immune cell dynamics, and survival outcomes.

We conducted a prospective cohort study of 500 adults with advanced solid tumors initiating immune checkpoint inhibitor therapy, followed for up to 60 months. Sleep quality was assessed longitudinally using the Pittsburgh Sleep Quality Index at baseline and during follow-up. Circulating immune cell subsets were measured serially. Longitudinal changes in sleep quality and immune cell subsets according to exposure classification were analyzed using mixed-effects models. Progression-free and overall survival were evaluated using Kaplan-Meier methods and multivariable Cox proportional hazards models, with propensity score-based sensitivity analyses.

Patients receiving the structured sleep optimization program demonstrated greater longitudinal improvement in sleep quality during follow-up compared with patients receiving usual care. Program-associated longitudinal sleep improvement was aligned with greater longitudinal increases in cytotoxic immune-effector populations, including CD8 + T cells and natural killer cells, whereas regulatory immune subsets showed minimal between-group differences. Over extended follow-up, classification in the sleep optimization program group was associated with longer progression-free and overall survival after adjustment for demographic, clinical, and inflammatory covariates. These associations were consistent across sensitivity analyses and were not accompanied by higher rates of treatment-related adverse events.

These observational findings suggest that structured sleep optimization during immune checkpoint inhibitor therapy was associated with improved sleep quality, selective immune-effector remodeling, and favorable long-term clinical outcomes. Although causal inference cannot be established, the convergence of longitudinal sleep, immune, and survival associations supports further randomized and mechanistic investigations into sleep-focused supportive care during immunotherapy.