The immunogenomic difference between Asian and non-Asian esophageal squamous cell carcinoma (ESCC) patients: An analysis of the Cancer Genome Atlas (TCGA) cohort.

Abstract

27 Background: Recently reported global phase 3 trials of immune checkpoint inhibitor (ICI) versus second-line chemotherapy for esophageal cancer revealed that Asian population appear to obtain more benefit from ICI than non-Asian patients even in ESCC subgroups. Whether this observation could be explained by the immunogenomic difference between Asian and non-Asian ESCC remains uncertain. Methods: We retrieved the data of genetic alterations and gene expression profiling from ESCC patients of TCGA dataset, and compared the mutational profiles, immune subtypes, composition of immune cell infiltrates, and T cell-related signatures between Asian and Non-Asian patients with ESCC. Abundance of immune cell infiltrates were estimated by averaging expression values of the corresponding immune cells’ transcriptomic markers defined by Danaher et al. (J Immunother Cancer. 2017; 5:18.). The 6 immune subtypes were adopted from Thorsson et al (Immunity. 2018;48(4):812-830). The T-cell related signatures were determined by averaging the corresponding genes' expression values following previous reports. Results: We retrieved 93 patients with ESCC (Asian: non-Asian= 45: 48) from TCGA database. There is no statistical difference in overall survival between Asian and non-Asian ESCC patients. Higher mutation frequencies of TP53, NFE2L2, ZNF750, and lower mutation frequency of SMARCA4 were seen in Asian patients than in non-Asian patients. As for the immune contexture, we found that the composition of immune cell infiltrate, the distribution of immune subtypes, and a variety of T cell-related gene signatures including the 6-gene interferon-gamma signature, the 10-gene interferon-gamma signature defined by Merck or by Ribas et al, and the 13-gene inflammatory signature defined by Gajewski et al, were not significantly different between Asian and non-Asian groups. Conclusions: Our analysis failed to identify statistically significant difference in the immunogenomics of ESCC tumors between Asian and non-Asian patients in the TCGA cohort. Further immunogenomic studies focusing on patients from Asian countries with high ESCC prevalence are warranted.