• Novel Signature : We introduce a novel immunosuppression-associated lncRNA signature (ISLncSigs) for predicting NSCLC patient survival. • Independent Predictive Power : ISLncSigs demonstrates strong predictive capability for NSCLC survival, independently of other clinical factors. • Immunotherapy Sensitivity : High-risk NSCLC patients, identified by ISLncSigs, exhibit enhanced sensitivity to immunotherapy. • Chemotherapy Response : Certain chemotherapy drugs show increased effectiveness in the high-risk group, potentially guiding treatment decisions. • Immune Function Insights : The study uncovers downregulated immune-related functions in the high-risk group, shedding light on the NSCLC microenvironment. • Clinical Implications : ISLncSigs have significant potential to impact NSCLC treatment strategies and clinical decisions. Non-small cell lung cancer (NSCLC) is influenced by the immune regulation mediated by lncRNAs. However, the understanding of immunosuppression-associated lncRNAs and their clinical significance in NSCLC is still limited. We utilized RNA-seq and clinical data from the TCGA database to investigate lncRNAs associated with immunosuppression in NSCLC. Univariate Cox regression was employed to identify prognostic immunosuppression-associated lncRNAs, and the immunosuppression-associated lncRNA signatures (ISLncSigs) were established using LASSO regression analysis. Differentially expressed genes were subjected to enrichment analysis. The signatures were further evaluated for their impact on immune function, immunotherapy, TMB, and response to chemotherapy drugs in high-risk and low-risk groups. Finally, the prognostic value of the signature was validated in the IMvigor210 cohort. The ISLncSigs exhibited strong predictive capability for NSCLC patient survival and showed independence from other clinical characteristics. The high-risk group displayed significant downregulation of immune-associated functions, including APC co-inhibition, CCR, T cell co-inhibition, immune checkpoint, and HLA expression. The poor prognosis observed in the high-risk group was associated with HLA functional loss, increased tumor immune evasion, and pathways associated with cisplatin resistance. However, the high-risk group demonstrated enhanced sensitivity to immunotherapy. Furthermore, certain chemotherapeutic agents (vinorelbine, parthenolide, paclitaxel, and gemcitabine) exhibited lower IC50 values in the high-risk group. Immunosuppression-associated lncRNAs can be utilized to construct a prognostic signature for NSCLC. This signature provides valuable insights into the role of lncRNAs in the NSCLC microenvironment and has potential implications for guiding clinical treatment strategies.
Yu et al. (Thu,) studied this question.