Predictive value of the biomarker of peripheral blood of NSCLC patients responding to anti-PD-1 treatment

Abstract

Abstract Background The introduction of anti-PD-1 antibody has greatly improved the clinical outcomes of patients with non-small cell lung cancer(NSCLC). Here we retrospectively analyzed the efficacy of PD-1 antibody-based therapy in patients with locally advanced un-operable or metastatic NSCLC patients and report an association between peripheral blood biomarkers with clinical response in these patients. Methods We conducted a single-center study by including medical record data for NSCLC patients treated with PD-1 antibody first-line or posterior-line either as monotherapy or in combination with chemotherapy. The patients enrolled from 2020 to 2022. Dynamic evaluation of multiple Th1 and Th2 cytokines in the blood serum, as well as analysis of the phenotype of T cells from peripheral blood, was conducted to explore the correlation between cytokines levels, T cell phenotype, and clinical response. Results 88 stage IIIA-IV NSCLC patients were enrolled. 60(68.18%) patients achieved partial response(PR), 13 (14.77%) patients were stable(SD) and 15(17.05%) patients had progressed disease (PD). The disease control rate (DCR) was 82.95%. Our results suggested a significant reduction (P = 0.002, P < 0.005) of lymphocyte absolute counts after treatment in the patients with disease progression(PD). Higher levels of IFN-γ(P = 0.023,P < 0.05), TNF-α(P = 0.00098,P < 0.005 ), IL-4 (P = 0.0031 ,P < .0.005), IL-5 (P = 0.0015,P < 0.005) and IL-10 ( P = 0.036 ,P < 0.05) were detected in peripheral blood prior to the treatment in PR group comparing with PD group.. Besides, those patients with high IL-5、IL-13、IL-4、IL-6、IFN-γ and TNF-α(> 10ng/ml) had superior PFS than those with low IL-5、IL-13、 IL-4、IL-6、IFN-γ and TNF-α(< 10ng/ml). Moreover, the expression of PD-1 expression on CD8+Tcells was positive associated with the clinical response between response patients (PR)and non-response(SD + PD)patients(P = 0.042, P < 0.05). Conclusions The findings of this study imply that the decrease in absolute blood lymphocyte counts after treatment is correlated to the progression of the disease. It is possible that serum cytokine concentrations can forecast the effectiveness and survival rate of anti-PD-1 blockade therapy in NSCLC patients. In addition, the expression of PD-1 expression on CD8+Tcells was positive associated with the better clinical response as well. The findings of our study indicated the potential of peripheral blood biomarkers analysis to offer predictive value of PD-1-targeted treatments to NSCLC patients. Large prospective studies need to further clarify the value of these biomarkers.