Identification of CXCL5 expression as a predictive biomarker associated with response and prognosis of immunotherapy in patients with non-small cell lung cancer

Abstract

Background: The breakthrough of immunotherapy has revolutionized the treatment of non-small cell lung cancer (NSCLC). However, only a limited part of patients could derive clinical benefits. To study how immune microenvironment (IME) of patients could influence the therapeutic efficacy of immunotherapy, we evaluated the response patterns of NSCLC patients treated with PD-1 inhibitors and analyzed the molecules related to prognosis and efficacy of immunotherapy. Methods: Tumor samples were collected from 47 NSCLC patients treated with PD-1 inhibitors. RNA expressions of tumor immune-related 289 genes were analyzed using NanoString nCounter. Immune infiltration and correlation between clinical information and expression of immune-related genes were assessed. Results: Unsupervised clustering analysis revealed two groups infiltrated with different immune cells and differentially expressed genes (DEGs) including CXCL5, CXCL9, IDO1, and LAG3 were found between groups. Stratification based on DEGs indicated that the group with high expression of CXCL5 was characterized by neutrophils. Univariate and multivariate Cox analysis further demonstrated that CXCL5 mRNA expression was positively associated with worse progression free survival (PFS). Logistic analyses indicated high CXCL5 was associated with worse response to immunotherapy. Conclusions: CXCL5 may be a potential biomarker for prognosis and responsiveness to immunotherapy and may be a novel preventive and therapeutic target for NSCLC.