Low on-treatment levels of serum soluble CD8 (sCD8) predict better outcomes in advanced non-small cell lung cancer patients treated with atezolizumab

BACKGROUND: Immunotherapy has changed the paradigm of treating non-small cell lung cancer (NSCLC). But, selecting patients who will achieve long-term benefits from treatment remains unsatisfactory. Here, we investigated the possible use of the soluble form of CD8 antigen (sCD8) in predicting durable disease control after PD-1/PD-L1 blockade. CD8 is a marker of the cytotoxic T lymphocytes. Its soluble form (sCD8) is secreted under activation of the immune system but also has immunosuppressive properties. The data about serum sCD8 in patients dosed with anti-PD-1/PD-L1 drugs are lacking. METHODS AND RESULTS: We included 42 NSCLC patients and collected samples at baseline and for the first 3 months of atezolizumab immunotherapy. The serum sCD8 concentrations were measured with the ELISA kit and correlated with treatment outcomes. Patients with durable (≥ 12 months) disease control presented lower serum sCD8 than those without long-term benefits. The sCD8 levels measured at the end of cycle 2 (sCD8.2) were the earliest time point that successfully differentiated patients (3.76 vs. 9.68 ng/mL, respectively, p < 0.001). Individuals with low sCD8.2 (≤ 4.09 ng/mL) presented longer progression-free survival (HR = 0.061, p < 0.001) and overall survival (HR = 0.104, p < 0.05) compared to individuals with high sCD8.2 (median values unreached vs. 4.4 months and 14.4 months for PFS and OS, respectively). CONCLUSIONS: Serum sCD8 could be an early biomarker of durable disease control after anti-PD-L1 treatment. Higher sCD8 in patients with worse outcomes could suggest the inhibitory effect of sCD8 on cytotoxic T-cells activation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00262-023-03377-8.