Characterization of Pre- and Post-treatment Soluble Immune Mediators and the Tumor Microenvironment in NSCLC Patients Receiving PD-1/L1 Inhibitor Monotherapy

Abstract Background Despite the favorable therapeutic efficacy observed with ICI monotherapy, the majority of non-small cell lung cancer (NSCLC) patients do not respond. Therefore, identifying patients who could optimally benefit from ICI treatment remains a challenge. Methods Among 183 patients with advanced or recurrent NSCLC who received ICI monotherapy, we analyzed 110 patients whose pre- and post-treatment plasma samples were available. Seventy-three soluble immune mediators were measured at ICI initiation and 6 weeks later. To identify useful biomarkers, we analyzed the association of pre-treatment levels and post-treatment changes of soluble immune mediators with survival of patients. The associations of pre-treatment or on-treatment biomarkers with irAE development, PD-L1 expression, CD8 + TIL density, and neutrophil to lymphocyte ratio (NLR) were also analyzed. Results Pre-treatment biomarkers included 6 immune mediators (CCL13, CCL19, CCL21, CXCL5, CXCL10 and TNFSF13B) whereas on-treatment biomarkers included 8 immune mediators (CCL7, CCL19, CCL23, CCL25, IL-10, IL-32, IL-34 and TNFSF12). IrAE development was associated with post-treatment change in CCL23. PD-L1 expression was associated with the pre-treatment levels of TNFSF13B and the post-treatment change in CCL25. CD8 + TIL density was associated with the pre-treatment CXCL10 level, whereas NLR was correlated with pre-treatment levels of CCL13 and CCL17. Conclusion We identified several possible pre-treatment and on-treatment biomarkers in patients with NSCLC who received ICI monotherapy. Some of these biomarkers were associated with other possible predictors, including irAE development, PD-L1 expression, CD8 + TIL density and NLR. Further large-scale studies are needed to establish biomarkers for patients with NSCLC who received ICI monotherapy.