Early increase of CD103 expression on peripheral PD-1+ CD8+ T cells predicts response to nivolumab in advanced esophageal squamous cell carcinoma

Nivolumab has become a standard treatment for advanced or recurrent esophageal squamous cell carcinoma (ESCC). However, reliable blood-based biomarkers predictive of response remain undefined. We investigated dynamic changes in peripheral PD-1+ CD8+ T-cell subsets during nivolumab therapy and evaluated their clinical significance. Fifty-seven patients with advanced or recurrent ESCC treated with nivolumab were enrolled in this retrospective observational study. Peripheral blood mononuclear cells were collected before treatment and at 1, 2, and 4 weeks after initiation. Flow cytometric analyses evaluated the expression of CD103, CD45RA, Tim-3, LAG-3, TIGIT, and Ki-67 among nivolumab-binding PD-1+ CD8+ T cells. Associations between immunophenotypic changes, treatment response, survival outcomes, immune-related adverse events (irAEs), and nutritional/inflammatory indices were analyzed. The objective response rate was 24.6%, and the median overall survival (OS) was 11.7 months. CD103 expression among PD-1+ CD8+ T cells significantly increased after nivolumab initiation and was sustained up to 4 weeks. At 4 weeks, responders showed significantly higher CD103 frequency than non-responders (P = 0.00407). Patients with high CD103 expression demonstrated significantly improved OS (P = 0.0421), whereas progression-free survival was not significantly different. CD103 expression was not correlated with baseline nutritional or inflammatory markers. Responders more frequently experienced irAEs, particularly rash. Early elevation of CD103 expression among peripheral PD-1+ CD8+ T cells was associated with objective response and improved overall survival in patients with ESCC and may represent a minimally invasive exploratory biomarker during nivolumab therapy.