Immune signatures of patients with advanced non-small-cell lung cancer for efficacy prediction after immunotherapy.

BACKGROUND

Programmed cell death protein 1 ligand 1 (PD-L1) expression alone may not be the optimal predictor of immunotherapy (IO) efficacy in advanced non-small cell lung cancer (NSCLC). Evaluation of circulating immune signatures using mass cytometry is a promising technique for predicting IO response and prognosis. The utility of circulating immune signatures for efficacy prediction after IO in advanced NSCLC remains to be elucidated.

OBJECTIVES

To assess the feasibility of circulating immune cells and cytokines in predicting tumor response to IO in advanced NSCLC.

DESIGN

A prospective observational study.

METHODS

To investigate dynamic changes in immune signatures, blood specimens were prospectively collected from patients with NSCLC at baseline and following chemotherapy (C/T) and/or IO. Mass cytometry and enzyme-linked immunosorbent assay were used to characterize immune signatures and cytokine patterns to identify correlations between immune profiles and treatment efficacy.

RESULTS

The study enrolled 45 patients. The proportion of circulating natural killer (NK) cells and CD8 T cells significantly increased after IO alone treatment. Cell levels of PD-1CD8 T cells, PD-1CD4 T cells, TIM-3CD8 T cells, LAG-3 NK cells, and LAG-3CD8 T cells significantly decreased in patients with treatment response to IO alone. Tumor necrosis factor-alpha (TNF-α) levels significantly increased after IO alone treatment. Patients with high PD-1CD8 T cells before IO alone treatment had lower overall survival (OS) compared to those with low levels. Patients with high LAG-3CD8 T cells before chemotherapy plus immunotherapy treatment had lower OS compared to those with low levels.

CONCLUSION

Responses to IO in NSCLC were correlated with declines in specific exhausted T cells, suggesting that IO may exert therapeutical efficacy by decreasing circulating exhausted T cells, which were associated with poorer survival, while also increasing TNF-α. These results highlight the prognostic value of monitoring changes in circulating exhausted T cells to predict IO response and survival outcomes in advanced lung cancer.