Galectin-9-based immune risk score model helps to predict relapse in stage I–III small cell lung cancer

BACKGROUND: For small cell lung cancer (SCLC) therapy, immunotherapy might have unique advantages to some extent. Galectin-9 (Gal-9) plays an important role in antitumor immunity, while little is known of its function in SCLC. MATERIALS AND METHODS: By mean of immunohistochemistry (IHC), we tested the expression level of Gal-9 and other immune markers on both tumor cells and tumor-infiltrating lymphocytes (TILs) in 102 surgical-resected early stage SCLC clinical samples. On the basis of statistical analysis and machine learning results, the Gal-9-based immune risk score model was constructed and its predictive performance was evaluated. Then, we thoroughly explored the effects of Gal-9 and immune risk score on SCLC immune microenvironment and immune infiltration in different cohorts and platforms. RESULTS: In the SCLC cohort for IHC, the expression level of Gal-9 on TILs was statistically correlated with the levels of program death-1 (p=0.001), program death-ligand 1 (PD-L1) (p<0.001), CD3 (p<0.001), CD4 (p<0.001), CD8 (p<0.001), and FOXP3 (p=0.047). High Gal-9 protein expression on TILs indicated better recurrence-free survival (30.4 months, 95% CI: 23.7–37.1 vs 39.4 months, 95% CI: 31.6–47.3, p=0.009). The immune risk score model which consisted of Gal-9 on TILs, CD4, and PD-L1 on TILs was established and validated so as to differentiate high-risk or low-risk patients with SCLC. The prognostic predictive performance of immune risk score model was better than single immune biomarker (area under the curve 0.671 vs 0.621–0.644). High Gal-9-related enrichment pathways in SCLC were enriched in immune system diseases and rheumatic disease. Furthermore, we found that patients with SCLC with low immune risk score presented higher fractions of activated memory CD4 T cells than patients with high immune risk score (p=0.048). CONCLUSIONS: Gal-9 is markedly related to tumor-immune microenvironment and immune infiltration in SCLC. This study emphasized the predictive value and promising clinical applications of Gal-9 in stage I–III SCLC.