Variation of Peripheral Blood-based Biomarkers for Response of Anti-PD-1 Immunotherapy in Lung Cancer

Abstract The therapeutic regimen of immune checkpoint inhibitors (ICIs) has been a great achievement of elevated survival results in lung cancer, but only a small proportion of patients can benefit from it in the long term. Therefore, peripheral blood-based biomarkers which could effectively predict the efficacy of anti-PD-1/PD-L1 immunotherapy are crucial for selection of dosage regimen. Here we compared the performance of four machine learning models and chose lightGBM model to screen and analyze the most important biomarkers in peripheral blood. The results show that some peripheral immune cell subsets, serum inflammatory and immunological biomarkers are all valuable predictors of therapeutic responses and progression free survival (PFS). In analysis of immune cell subsets, biomarkers positively associated with benefit to immunotherapy are CD4+CD25+, CD3+CD56+and CD4/CD8, while PD-1+ on T cells plays a negative role. The results of inflammatory markers showed that most of them were correlated with disease progression. Moreover, the high expression of serum immunological biomarkers such as ΔCEA%, CYFRA21-1 and NSE may indicate that ICIs is not effective. Our above results provide some promising peripheral blood biomarkers for immunotherapy of lung cancer, and assist the management and therapeutic designing of patients.