Systemic inflammation influences the prognosis of patients with radically resected non‐small cell lung cancer and correlates with the immunosuppressive microenvironment

The impact of host condition on prognosis of non-small cell lung cancer (NSCLC) and the interaction between host and NSCLC remain unclear. This study investigated the association between systemic inflammation and prognosis and characteristics of radically resected NSCLC. This study consisted of a cohort study and an exploratory study of institutional prospective databases. All participants underwent video-assisted thoracoscopic lobectomy as the primary treatment. Systemic inflammation was assessed before surgery using the advanced lung cancer inflammation index and the systemic inflammation response index. Next-generation sequencing and multiplex immunofluorescence analysis were conducted to delineate tumor characteristics. In the cohort study including 1507 participants, high inflammation was associated with poor disease-free survival and overall survival before and after propensity score matching and in multivariable analysis. Systemic inflammation showed good prognostic value for stage IA-IB NSCLC, and the prognostic value diminished with upstaging of NSCLC. In the exploratory study including 217 adenocarcinomas, tumor microenvironment of high inflammation group showed a greater abundance of PDL1+ tumor cells and immune cells, which were independent from driver gene mutations and clinicopathological characteristics. Spatial analysis demonstrated a higher frequency of immune-suppressed cellular neighborhood, increased avoidance between immune cells and PDL1- tumor cells and compromised immune killing and presentation in tumor microenvironment of high inflammation group. Systemic inflammation showed limited association with genomic mutations. Systemic inflammation may influence the prognosis of NSCLC at both the systematic level and the local immune response. The correlation between high inflammation and immunosuppressive microenvironment indicates a novel thread for anticancer treatment.