Changes in Serum Interleukin-8 Levels Predict Response to Immune Checkpoint Inhibitors Immunotherapy in Unresectable Hepatocellular Carcinoma Patients.

BACKGROUND

Effective biomarkers are needed to predict the efficacy of immune checkpoint inhibitors (ICIs) therapy in hepatocellular carcinoma (HCC). We evaluated the early changes in serum interleukin-8 (IL-8) levels as a biomarker of response to ICIs in patients with unresectable HCC.

METHODS

Eighty patients who received ICIs therapy alone or in combination with other treatments for unresectable HCC were included. Serum was collected at baseline and 2-4 weeks after the first dose. Serum IL-8 levels were measured using by ELISA.

RESULTS

In the progressive disease (PD) group, serum IL-8 levels increased significantly before the second dose of ICIs therapy compared with baseline levels ( < 0.001). Early changes in serum IL-8 levels were significantly associated with the response to ICIs therapy ( < 0.001). A cutoff value of 8.1% increase over the baseline most effectively predicted the response to ICIs. Increases in serum IL-8 levels > 8.1% indicated the uselessness of ICIs immunotherapy in patients with unresectable HCC. Patients with increases in serum IL-8 levels > 8.1% had significantly shorter overall survival (OS) and progression-free survival (PFS) than those with increases in serum IL-8 levels ≤ 8.1% ( < 0.001). Increases in serum IL-8 levels > 8.1% were independent prognosticators of worse OS ( = 0.003) and PFS ( < 0.001).

CONCLUSION

Early changes in serum IL-8 levels, measured only 2-4 weeks after starting therapy, could predict the response to ICIs therapy, as well as OS and PFS of patients with unresectable HCC. Increases in serum IL-8 levels > 8.1% indicated the uselessness of ICIs immunotherapy and predicted worse OS and PFS.