Interplay between immune infiltration and tumor progression and survival in non-small cell lung cancer: An analysis of institutional and public data.

Abstract

8538 Background: In many types of cancer, infiltration of tumor by immune cells, as a reflection of the immune response against the tumor, is thought to play a critical role in clinical outcome. Tumors, however, tend to evade the immune response as they progress. In this study, we characterize the interplay between immune infiltration and tumor progression and survival in non-small cell lung cancer (NSCLC). Methods: We performed histologic immune profiling and microarray expression analysis on primary tumor specimens from 275 NSCLC patients (PR: PROSPECT trial) as well as RNA-Seq expression analysis on biopsy specimens from 50 patients with advanced NSCLC (B2: BATTLE-2 trial). RNA-Seq data from the TCGA lung cancer project was also analyzed. Immune Infiltration Score (IIS) was computed from the expression data using the Estimate package in R. Immune Suppression Score (ISS) was defined as the difference between the mean of CD3, CD4, CD8, FOXP3, and PD1 counts in the periphery and core of the tumor. Results: Tumor IIS is correlated (all p < 0.0005) with tumor immune infiltration as measured by inflammatory cell count on frozen tumor or several immune marker counts in tumor core. IIS is positively associated with survival (p = 0.04) independently of age (p = 0.008) and stage (p = 8e-10). IIS in the top half is associated with higher median survival vs. bottom half (10.2 vs 2.2 months, p < 0.0001) in B2. In TCGA lung adenocarcinoma samples, IIS is higher in stage I/II disease vs stage III/IV (p = 0.003). For all immune markers in PR samples, periphery of the tumor on average has higher counts vs tumor core (p < 0.0011), and this difference (suppression score) is higher in stage III/IV samples vs stage I/II for CD3, CD4, and CD8 (all p < 0.04) and for FOXP3 and PD1 (p < 0.1). ISS is negatively associated with survival (p = 0.02) independently of age (p = 0.06) and stage (p < 0.0001). Conclusions: As NSCLC tumors progress, immune infiltration in the periphery of the tumor increases while infiltration in the core decreases, reflecting increasing immune suppression. Tumor immune infiltration and suppression, as measured by IIS and ISS, are significant predictors of survival, independently of age and stage.