High Serum IgA Identifies Poor Responders to Immune Checkpoint Inhibitors in Patients with Unresectable Esophageal...

Immune checkpoint inhibitors (ICIs) have become a standard first-line treatment for unresectable esophageal squamous cell carcinoma (ESCC). However, a substantial proportion of patients have early disease progression. Reliable pretreatment biomarkers capable of predicting ICI efficacy are urgently needed. Immunoglobulin A (IgA) has been implicated in shaping an immunosuppressive tumor microenvironment, yet its clinical relevance in ESCC remains unclear.

Serum IgA levels were measured in patients who had unresectable ESCC treated with first-line ICI-based therapy (n = 20) and compared with those in disease control subjects (non-ICI [n = 16] vs resectable ESCC [n = 26]) and healthy control subjects (n = 58). Associations between pretreatment serum IgA levels, survival times, and clinicopathologic variables were analyzed. The patients in each cohort were stratified into high- and low-IgA groups using cohort-specific median values.

Serum IgA levels were significantly higher in all the ESCC patient groups than in the healthy control subjects. In the ICI-treated group, high pretreatment serum IgA was significantly associated with shorter progression-free survival (hazard ratio, 9.26; 95% confidence interval, 1.96-43.7; P = 0.005). No correlation between serum IgA and prognosis was observed in the non-ICI and resectable ESCC groups, indicating ICI-specific relevance. Pretreatment serum IgA did not correlate with clinicopathologic factors, including tumor markers and immune-related adverse events.

High pretreatment serum IgA may serve as a novel, minimally invasive biomarker predicting poor response to ICI therapy in unresectable ESCC. Serum IgA assessment could support treatment decision-making and patient stratification in this era of expanding immunotherapy use.