Exploring the role of TIGIT in patients with Small Cell Lung Cancer as a novel predictor of prognosis and immunotherapy response

Abstract

Background: T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) is a novel immune checkpoint playing a crucial role in immunosuppression and immune evasion. This study aims to elucidate the expression patterns, characteristics, and possible mechanisms of TIGIT in small cell lung cancer (SCLC). Methods: TIGIT expression was analyzed across various cancers and normal tissues using The Cancer Genome Atlas (TCGA). Transcriptomic data from SCLC patients, sourced from the Gene Expression Omnibus (GEO) and literature, were analyzed to assess TIGIT-related characteristics. Immunohistochemistry (IHC) was used to verify TIGIT expression in post-surgical and advanced SCLC samples, focusing on expression characteristics, prognostic value, and treatment response. Results: TIGIT was significantly overexpressed in various tumors, including SCLC (p < 0.05). Higher expression was associated with better overall survival (OS) (p < 0.05). Notably, a significant positive correlation was observed between TIGIT expression and immune-related metagenes, such as HCK, interferon, and LCK (p < 0.05). Immune infiltration analysis revealed a strong positive correlation between TIGIT expression and immune score in multiple cohorts. Additionally, TIGIT expression correlated positively with immune cells, including CD8 T cells, cytotoxic lymphocytes, and B cells (p < 0.05), and multiple immune checkpoints like BTLA, ICOS, and LAG3 (p < 0.05), while it had a significant negative correlation with the TIDE score (p < 0.05). In the validation section, patients with high TIGIT expression showed significantly prolonged disease-free survival (DFS) and OS (p < 0.05), and demonstrated a better response to adjuvant chemotherapy (ACT) and immunotherapy. Conclusion: TIGIT serves as a biomarker in SCLC, with its high expression indicating favorable prognosis and treatment response. These effects may be due to TIGIT’s unique immune landscape and its association with other immune checkpoints.