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

Abstract

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.

• Authors: Anqi Lin, Hongman Zhang, Hui Meng, Ze Deng, Tianqi Gu, Peng Luo, Jian Zhang
• Journal: Frontiers in immunology (Front Immunol) Vol. 12 Pg. 667875 ( 2021) ISSN: 1664-3224 [Electronic] Switzerland
• PMID: 34603277 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Lin, Zhang, Meng, Deng, Gu, Luo and Zhang.

Chemical References

• Biomarkers, Tumor
• Immune Checkpoint Inhibitors
• Tumor Necrosis Factor-alpha

Topics

• Biomarkers, Tumor
• Carcinoma, Non-Small-Cell Lung (drug therapy, etiology, metabolism, mortality)
• Humans
• Immune Checkpoint Inhibitors (pharmacology, therapeutic use)
• Lung Neoplasms (drug therapy, etiology, metabolism, mortality)
• Models, Biological
• Molecular Targeted Therapy
• Mutation
• Prognosis
• Signal Transduction (drug effects)
• Treatment Outcome
• Tumor Microenvironment (drug effects, immunology)
• Tumor Necrosis Factor-alpha (metabolism)