Abstract
Introduction:
Non-small cell lung cancer (NSCLC) leads to substantial challenges in cancer treatment owing to its diverse histological and molecular characteristics. Immune checkpoint inhibitors (ICIs) have revolutionized the management of NSCLC. Nevertheless, there exist limitations in utilizing biomarkers, like PD-L1 expression for predicting the efficacy of ICIs, necessitating novel biomarkers.
Methods
We investigated the relationship between peripheral blood T cell subsets, cytokines, and efficacy of ICIs in patients who received ICIs as their first-line treatment for pathologically confirmed locally advanced or metastatic NSCLCs. Propensity score matching (PSM) was employed to match individuals between the response and non-response groups. Subsequently, peripheral blood T lymphocyte profiles and cytokine subsets were measured using flow cytometry. Mann-Whitney and Kruskal-Wallis tests were used for intergroup analysis before, after, and during treatment. Log-rank regression and Cox regression models were used to analyze survival and conduct multivariate analysis, respectively.
Results
Between July 1, 2021, and December 31, 2023, there were 470 patients with clinical stage IIIB to IV NSCLC. After applying the inclusion criteria, a post-propensity score-matching analysis was performed on 102 patients. The median progression-free survival (PFS) was 14.30 months. These subsets included activated CD4+ T cells (HLA-DR+)/CD4% (P = 0.0170), memory CD8+ T cells/CD8% (P = 0.0115), activated CD8+ T cells (CD38+)/CD8% (P = 0.0020), and activated CD8+ T cells (HLA-DR+)/CD8% (P < 0.0001). Changes in cytokine levels before and after treatment with ICIs indicated that IL-6 levels showed a downward trend in the responder group. Additionally, our analysis revealed that an increased ratio of activated CD8+ T cells (CD38+)/CD8% (average PFS: 22.207m vs. 15.474m) and a decreased ratio of activated CD8 + T cells (HLA-DR+)/CD8% after treatment (mean PFS: 17.729m vs. 25.662m) are associated with longer PFS. Multivariate analysis unveiled that alterations in the abundance of activated CD8+ T cells were independent prognostic factors for PFS in patients with advanced NSCLC.
Conclusions
This study emphasizes the significance of peripheral blood biomarkers in predicting the efficacy of ICIs in NSCLC. Activated CD8+T cells (CD38+) represent a promising biomarker for response to ICIs, providing insights into personalized treatment strategies. Further prospective studies are warranted to validate findings and improve the outcome of NSCLC.