P66.05 Correlation Between Expression of Immune Cell-Related Molecular Markers and Prognosis in Small Cell Lung Cancer (SCLC)

Abstract

Current retrospective studies have found that the prognosis of patients with small cell lung cancer (SCLC) after surgical resection varies greatly. At present, the biological factors relevant to tumor immune microenvironment (TIME) that affect the prognosis of patients with SCLC remain to be explored. Content of 22 types of immune cells in TIME was estimated by CIBERSORT in a public dataset containing 77 postoperative SCLC patients. Correlation of each type of immune cells with overall survival (OS) was analyzed by univariate and multivariate Cox regression analysis. Vital cytokines and their receptors which correlated with gamma delta T cells (γΔT) and resting NK cells whose abundance significantly influence OS derived from public data analysis were detected at transcriptional level in tissue samples of 48 prognosis-based paired SCLC patients in our institute. Markers of activated NK cells, T cells, B cells, and immune effector molecules were also detected. Each marker was fitted into univariable Cox regression model. Molecular markers correlated with resting NK cells and γΔT and molecules whose coefficient reached statistical significance in univariate analysis were combined with clinicopathological factors for multivariate survival analysis. Univariate Cox regression analysis for external dataset showed that high relative proportion of follicular helper T cells (Tfh) is protective for OS (HR 1.30e-05, 95% CI: 3.2e-09-0.52, P = 0.008), while high relative proportion of γ Δ T cells (HR 4e+03, 95% CI 6.5-2.5e+06, P=0.011) and resting NK cells (HR 1.2e+10, 95% CI 200-7.5e+17, P=0.011) were hazardous for OS. Significant distinct disease-free survival (DFS) and OS was observed between the two paired groups in our internal cohort (DFS: P=1.00e-12; OS: P=2.05e-09), but there was no significant difference in clinical characteristics such as age, gender, clinical stage, treatment methods between the two groups. However, it was found that the expression of IL17RB was significantly higher in the poor prognosis group (P=0.015), while the expression of interferon γ(IFNG) and perforin (PRF1) was significantly lower in the poor prognosis group (IFNG: P=0.045; PRF1: P=0.013). Univariable Cox regression analysis confirmed that high expression of IL17RB was hazardous for shorter DFS, while high expression of activating receptor of NK cells (NCR1, NKG7), markers of effector T cells (CD8A) and cytotoxic molecules (PRF1, GZMB, GZMH) and IFNG were favorable for DFS. Among these molecules, influence on OS was also significant for NKG7, PRF1 and GZMB. Multivariable Cox regression analysis combining clinicopathological and immunological factors identified high expression of IL6 mRNA was hazardous for both DFS and OS independent of clinicopathological factors. Abundance of NK cells and T cells in TIME significantly affected the postoperative DFS of SCLC patients. Content of NK cells in TIME also significantly influenced OS of resected SCLC patients. The prognosis of patients with high expression of IL6 and IL17RB mRNA was extremely dismal, which might be explained by impairment of NK cell activity and γΔT polarization.