Peripheral blood IFN-γ–producing T-cell subsets and soluble IL-2 receptor as independent prognostic biomarkers in NSCLC treated with immune checkpoint inhibitor–based therapy

Immune checkpoint inhibitor(ICI)–based therapy has revolutionized non-small-cell lung cancer (NSCLC) treatment, yet reliable biomarkers for monitoring immune response in real time remain elusive.

In NSCLC patients, lymphocyte counts and function through interferon (IFN)-γ secretion in CD4⁺, CD8⁺ T cells and NK cells were detected prior to therapy, at day 21 post therapy by flow cytometry. We also dynamically assessed alterations in the cytokines tumor necrosis factor-alpha, interleukin (IL)-2R, IL-6 and IL-8, establishing the clinical utility in predicting ICI-based therapy outcomes.

The study found that different therapies induced distinct patterns of immune remodeling. ICI-based therapy significantly increased IFN-γ secretion by CD4 + and CD8 + T cells (both P < 0.05) and decreased sIL-2R levels (P < 0.01). Radiotherapy activated T cell function but caused marked lymphocytopenia (P < 0.001). Chemotherapy did not produce significant immune fluctuations. Multivariate analysis confirmed that high IFN-γ + CD4 + T cell levels (HR = 0.19, P = 0.014) and high sIL-2R levels (HR = 29.03, P < 0.001) were independent prognostic factors for progression-free survival (PFS). The nomogram integrating these indicators demonstrated excellent predictive performance (C-index = 0.867).

This study demonstrated the value of peripheral blood immune-function indicators for monitoring treatment response and showed that a composite model based on IFN-γ CD4⁺ T cells and sIL-2R served as an effective tool for stratifying and prognosticating NSCLC patients.