Objective  Immunotherapy has brought durable clinical benefits to some patients with non-small cell lung cancer (NSCLC), but how to accurately screen potential beneficiaries of immunotherapy remains an urgent issue to be addressed in clinical practice. This study aimed to explore the characteristics of peripheral blood cytokines in NSCLC patients who achieved durable clinical benefits from immunotherapy.

Methods  Baseline and post-treatment peripheral blood specimens of patients diagnosed with stage Ⅲ~Ⅳ NSCLC and scheduled for immunotherapy at Guangdong Provincial People's Hospital from September 2020 to October 2021 were collected, and the levels of 34 cytokines were detected. Patients were classified into the durable clinical benefit (DCB) group and the non-durable benefit (NDB) group based on the efficacy of immunotherapy, and the differences in cytokine levels between the two groups and their relationship with survival prognosis were analyzed.

Results  A total of 53 baseline peripheral blood samples and 13 pairs of post-treatment blood samples were collected for cytokine detection and analysis. In the immunotherapy combined with chemotherapy group, the baseline CCL4 level in the DCB group was significantly higher than that in the NDB group (mean DCB: 41.11 pg/mL vs. NDB: 26.17 pg/mL, P = 0.023). The ROC curve constructed using CCL4 had an AUC of 0.74 (95% confidence interval 0.55~0.93, P = 0.024), and the Youden index determined the critical value of CCL4 to be 24.04 pg/mL. The progression-free survival (PFS) of the high baseline CCL4 level group was significantly longer than that of the low baseline CCL4 level group (median PFS: 24.4 months vs. 5.9 months, P = 0.009), and the overall survival time (OS) was also significantly prolonged (median OS: 42.6 months vs. 13.1 months, P = 0.026). Multivariate Cox regression analysis indicated that the baseline CCL4 level was an independent prognostic factor for OS (P = 0.040). By comparing the changes in cytokines before and after immunotherapy, the level of IL1RA in the NDB group significantly increased after treatment, and the difference in the levels of IL1RA before and after treatment between the DCB group and the NDB group was statistically significant (P = 0.017). The level of IL17A in the NDB group exhibited an upward trend after treatment, and the levels of CCL11 and CXCL12 in the DCB group showed an increasing tendency after treatment.

Conclusion  A high baseline CCL4 level is associated with better clinical benefits from immunotherapy combined with chemotherapy. Elevated levels of IL1RA and IL17A after treatment may indicate a poor immune response, while elevated levels of CCL11 and CXCL12 may be related to sustained clinical benefits. Baseline cytokine levels and their dynamic changes after treatment can assist in screening patients who will benefit from sustained clinical benefits from immunotherapy, optimize stratified treatment strategies, and are potential biomarkers of immune efficacy.