Prognostic value of immunosuppression scores in patients with esophageal squamous cell carcinoma: a multicenter study

Introduction: The prognostic impact of human leukocyte antigen-E (HLA-E) expression and the proportion of natural killer (NK) cells in esophageal squamous cell carcinoma (ESCC) was investigated.

Methods: This study retrospectively evaluated 397 ESCC patients across two centers. The cumulative incidence of recurrence (CIR) and the incidence of tumor-related death (CID) were analyzed in various groups. An immunosuppression score (ISS) was developed based on HLA-E expression and NK cell proportion. Differences between groups were adjusted using inverse probability treatment weighting (IPTW). The factors influencing cancer-specific survival (CSS) and recurrence-free survival (RFS) were also examined.

Results: Patients with low HLA-E expression had significantly higher five-year CIR and CID compared to those with high expression (CIR: 20.7% vs. 45.1%, CID: 19.3% vs. 40.1%; p< 0.001). Similarly, NK cell-positive patients had significantly better five-year CIR and CID than NK cell-negative patients (CIR: 16.3% vs. 59.6%, CID: 13.9% vs. 53.7%; p < 0.001). The Sankey diagram indicated that the low ISS group had a lower recurrence and tumor-related mortality rate (p < 0.05). After IPTW adjustment, the low ISS group showed improved five-year RFS (80.1% vs. 35.4%, p < 0.001) and five-year CSS (82.3% vs. 42.5%, p < 0.001) compared to the high ISS group.

Conclusions: ESCC with different ISS statuses represents two distinct biological subtypes, underscoring the need for personalized treatment strategies tailored to varying tumor behaviors.