Peripheral Blood Lymphocyte Subsets Predict the Efficacy of Immune Checkpoint Inhibitors in Non-Small Cell Lung
Kang Miao1, Xiaotong Zhang1, Hanping Wang1
1Department of Pulmonary and Critical Care Medicine, Peking Union Medical Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
Background:
Non-small cell lung cancer (NSCLC) has entered the era of immunotherapy. However, only partial patients were able to benefit from immune checkpoint inhibitors (ICIs). Currently, biomarkers for predicting patients' response to ICIs are primarily tumor tissue dependent and have limited accuracy. There is an urgent need to explore peripheral blood-based biomarkers to predict the efficacy and safety of ICI therapy.
Methods:
To explore the correlation between lymphocyte subsets and the efficacy and safety of ICIs, we retrospectively analyzed peripheral blood lymphocyte subsets and survival prognosis data of 136 patients with stage IV NSCLC treated with ICIs.
Results:
The two factors that had the greatest impact on the prognosis of patients with NSCLC treated with ICIs were CD4+CD45RA- T cell (HR = 0.644, P = 0.047) and CD8+ T/lymphocyte (%) (HR = 1.806, P = 0.015). CD4+CD45RA- T cell showed excellent predictive efficacy (AUC = 0.854) for ICIs monotherapy, with a sensitivity of 75.0% and specificity of 91.7% using CD4+CD45RA- T cell >311.3 × 106/L as the threshold. In contrast, CD8+ T/lymphocyte (%) was only associated with the prognosis but had no predictive role for ICI efficacy. CD4+ T cell and its subsets were significantly higher in patients with mild (grades 1-2) immune-related adverse events (irAEs) than those without irAEs. CD8+CD38+ T cell was associated with total irAEs and severe (grades 3-4) irAEs but was not suitable to be a predictive biomarker.
Conclusion:
Peripheral blood CD4+CD45RA- T cell was associated with the prognosis of patients with NSCLC applying ICIs, whereas CD8+CD38+ T cell was associated with irAEs and severe irAEs.
Insights
Peripheral blood CD4+CD45RA- T cells can predict immunotherapy response in non-small cell lung cancer (NSCLC) patients. This blood biomarker also correlates with immune-related adverse events, offering a new avenue for treatment monitoring.
Area of Science:
- Immunology
- Oncology
- Biomarker Discovery
Background:
- Immunotherapy with immune checkpoint inhibitors (ICIs) has advanced non-small cell lung cancer (NSCLC) treatment.
- However, predicting patient response to ICIs remains challenging due to reliance on tumor tissue biomarkers with limited accuracy.
- There is a critical need for peripheral blood-based biomarkers to predict ICI efficacy and safety in NSCLC.
Purpose of the Study:
- To investigate the association between peripheral blood lymphocyte subsets and the efficacy and safety of ICI therapy in patients with stage IV NSCLC.
- To identify novel blood-based biomarkers for predicting response and adverse events in NSCLC patients undergoing ICI treatment.
Main Methods:
- Retrospective analysis of 136 patients with stage IV NSCLC treated with ICIs.
- Evaluation of peripheral blood lymphocyte subsets and survival prognosis data.
- Assessment of predictive efficacy using receiver operating characteristic (ROC) curves and correlation with immune-related adverse events (irAEs).
Main Results:
- CD4+CD45RA- T cell count was a significant prognostic factor for ICI efficacy in NSCLC (HR=0.644, P=0.047) with high predictive accuracy (AUC=0.854).
- CD8+ T/lymphocyte ratio was associated with prognosis but not predictive of ICI efficacy.
- Elevated CD4+ T cell subsets correlated with mild irAEs, while CD8+CD38+ T cells were linked to overall and severe irAEs.
Conclusions:
- Peripheral blood CD4+CD45RA- T cells serve as a promising biomarker for predicting ICI efficacy in NSCLC patients.
- CD8+CD38+ T cells are associated with irAEs, suggesting their role in monitoring treatment toxicity.
- These findings highlight the potential of peripheral blood lymphocyte subsets as accessible biomarkers for personalized ICI therapy in NSCLC.
