Abstract
BACKGROUND: Immune checkpoint inhibitors (ICIs) significantly impact advanced non-small cell lung cancer (NSCLC) management, but predictive biomarkers for elderly patients remain controversial. This study aimed to assess peripheral immune cells as biomarkers for predicting ICI efficacy in elderly NSCLC patients. METHODS: This was an ambispective, observational study enrolling patients aged ≥ 65 years with advanced NSCLC treated with first-line ICI ± chemotherapy from January 2023 to August 2024 at Beijing Chest Hospital. Peripheral immune cell subsets were analyzed by flow cytometry at baseline and dynamically during treatment. Associations between clinical characteristics, immune cell profiles, and outcomes were assessed using Kaplan-Meier analysis, Cox regression, and Wilcoxon tests. RESULTS: A total of 34 patients were included in this study. Objective response rate and disease control rate were 41.2% and 97.1%, respectively. Median progression-free survival (PFS) was 10.3 months, while median overall survival (OS) was not reached. Patients responding to ICIs had significantly higher baseline percentages of CD3(+) T cells, CD3(+)CD8(+)Perforin(+) T cells, and CD3(+)CD8(+)Granzyme B(+) T cells. Higher baseline absolute counts of CD3(+) T cells and CD3(+)CD8(+) T cells were also significantly associated with longer OS. Post-treatment increases in the percentage of CD3(+)Perforin(+) T cells were associated with significantly longer OS (up vs. down: not reached vs. 15.1 months, p = 0.034). CONCLUSIONS: Peripheral cytotoxic T cell subsets may serve as promising biomarkers for predicting the efficacy of ICIs in elderly NSCLC patients. Dynamic monitoring of immune cell profiles could further enhance prognostic accuracy.