Seasonal timing of anti–PD-1 therapy and survival outcomes in a real-world Pan-Cancer Cohort

BACKGROUND: Circannual variation in immune function may influence the efficacy of immune checkpoint inhibitors (ICIs), yet clinical evidence regarding seasonal effects remains limited. METHODS: We retrospectively analyzed adults with metastatic solid tumors treated with anti - PD-1 monotherapy at a single center between 2015 and 2024. Seasons were defined by regional daylight patterns: summer (April - October) and winter (November - March). Primary endpoints were overall survival (OS) and progression-free survival (PFS). Kaplan - Meier estimates, log-rank tests, multivariable Cox regression, propensity score matching (PSM), and a 3-month landmark analysis were performed. RESULTS: Among 430 patients, 245 (57.0%) initiated ICIs in summer and 185 (43.0%) in winter. In the unmatched cohort, summer initiation was associated with longer PFS and OS. After PSM, 181 patients remained in each group, and the survival advantage persisted: median PFS was 6.2 versus 3.6 months (HR 0.72, 95% CI 0.56-0.91) and median OS was 21.5 versus 12.4 months (HR 0.74, 95% CI 0.58-0.94) for summer versus winter, respectively. Landmark and multivariable analyses confirmed these findings. CONCLUSIONS: Initiation of anti - PD-1 therapy during summer was associated with significantly improved survival, suggesting that seasonal modulation of host immunity may influence ICI outcomes.