Peripheral CD4+ T cell signatures in predicting the responses to anti-PD-1/PD-L1 monotherapy for Chinese advanced non-small cell lung cancer.

Limited benefit population of immune checkpoint inhibitors makes it urgent to screen predictive biomarkers for stratifying the patients. Herein, we have investigated peripheral CD4+ T cell signatures in advanced non-small cell lung cancer (NSCLC) patients receiving anti-PD-1/PD-L1 treatments. It was found that the percentages of IFN-γ and IL-17A secreting naive CD4+ T cells (Tn), and memory CD4+ T cells (Tm) expressing PD-1, PD-L1 and CTLA-4 were significantly higher in responder (R) than non-responder (NonR) NSCLC patients associated with a longer progression free survival (PFS). Logistic regression analysis revealed that the baseline IFN-γ-producing CD4+ Tn cells and PD-1+CD4+ Tm cells were the most significant signatures with the area under curve (AUC) value reaching 0.849. This was further validated in another anti-PD-1 monotherapy cohort. Conversely, high percentage of CTLA-4+CD4+ Tm cells was associated with a shorter PFS in patients receiving anti-PD-L1 monotherapy. Our study therefore elucidates the significance of functional CD4+ Tn and Tm subpopulations before the treatment in predicting the responses to anti-PD-1 treatment in Chinese NSCLC patients. The fact that there display distinct CD4+ T cell signatures in the prediction to anti-PD-1 and anti-PD-L1 monotherapy from our study provides preliminary evidence on the feasibility of anti-PD-1 and anti-PD-L1 combination therapy for advanced NSCLC patients.