TNF-Alpha Pathway Alternation Predicts Survival of Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer

Translational research on immune checkpoint inhibitors (ICIs) has been underway. However, in the unselected population, only a few patients benefit from ICIs. Therefore, screening predictive markers of ICI efficacy has become the current focus of attention. We collected mutation and clinical data from an ICI-treated non-small cell lung cancer (NSCLC) cohort. Then, a univariate Cox regression model was used to analyze the relationship between tumor necrosis factor α signaling mutated (TNFα-MT) and the prognosis of immunotherapy for NSCLC. We retrospectively collected 36 NSCLC patients (local-cohort) from the Zhujiang Hospital of Southern Medical University and performed whole-exome sequencing (WES). The expression and mutation data of The Cancer Genome Atlas (TCGA)-NSCLC cohort were used to explore the association between TNFα-MT and the immune microenvironment. A local cohort was used to validate the association between TNFα-MT and immunogenicity. TNFα-MT was associated with significantly prolonged overall survival (OS) in NSCLC patients after receiving immunotherapy. Additionally, TNFα-MT is related to high immunogenicity (tumor mutational burden, neoantigen load, and DNA damage response signaling mutations) and enrichment of infiltrating immune cells. These results suggest that TNFα-MT may serve as a potential clinical biomarker for NSCLC patients receiving ICIs.