Preliminary exploration of poor prognostic factor IL-33 and its involvement in perioperative immunotherapy in stage II-III lung squamous cell carcinoma: a retrospective cohort study

Background: Current knowledge about the prognostic role of interleukin-33 (IL-33) in lung squamous cell carcinoma (LUSC) remains limited, particularly in stage II-III patients. This study aimed to verify the correlation between IL-33 expression and poor prognosis in stage II-III LUSC patients at both gene and protein levels and to investigate the potential role of IL-33 blockade in combination with immune checkpoint inhibitors (ICIs) in perioperative immunotherapy. Methods: A retrospective analysis was conducted of 103 patients with stage II-III LUSC who underwent surgical resection at Tianjin Medical University Cancer Institute & Hospital from November 1, 2004, to November 30, 2006. Of these, 83 patients were included based on complete follow-up data, and were divided into a gene expression group (38 patients) and a protein expression group (45 patients). IL-33 expression was analyzed using real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC). The correlation between IL-33 expression and overall survival (OS) was assessed using Kaplan-Meier survival analysis. Additionally, IHC results from 20 patients were used to explore the correlation between IL-33, programmed death ligand 1 (PD-L1), and Ki-67 expression levels. The total follow-up time exceeded 60 months, and the study endpoint was OS. Results: Patients with high IL-33 expression had significantly shorter OS compared to those with low IL-33 expression, both at the gene (P=0.006) and protein expression (P=0.01). Logistic regression analysis confirmed IL-33 as an independent prognostic factor for poor survival in stage II-III LUSC (P-gene=0.04, P-protein=0.009). Additionally, a significant positive correlation was observed between the protein expression of IL-33 (P=0.03), PD-L1 (P<0.001), and Ki-67 (P=0.01), indicating that high expression of these markers is associated with worse prognosis. Conclusions: High IL-33 expression in cancer tissues is associated with poor prognosis in stage II-III LUSC. IL-33 blockade combined with ICIs may provide new treatment regimens and ideas for perioperative immunotherapy in stage II-III LUSC patients.