Host immune response index in gastric cancer identified by comprehensive analyses of tumor immunity. (2nd November 2017)

• Record Type: Journal Article
• Authors: Park, Charny; Cho, Junhun; Lee, Jeeyun; Kang, So Young; An, Ji Yeong; Choi, Min Gew; Lee, Jun Ho; Sohn, Tae Sung; Bae, Jae Moon; Kim, Sung; Kim, Seung Tae; Park, Se Hoon; Park, Joon Oh; Kang, Won Ki; Sohn, Insuk; Jung, Sin Ho; Kang, Myung-Soo; Kim, Kyoung-Mee
• Is Part Of: Oncoimmunology. Volume 6:Number 11(2017)
• Publication Date: 2017-11-02
• Subjects: biomarker -- EBV -- gastric cancer -- gene signature -- immune response -- prognosis -- PD-L1 -- prognosis -- survival -- tumor infiltrating lymphocyte; Tumors -- Immunological aspects -- Periodicals; Neoplasms -- therapy -- Periodicals; Immunotherapy -- Periodicals; 616.994
• DOI: 10.1080/2162402X.2017.1356150
• Languages: English
• ISSNs: 2162-402X

Abstract

ABSTRACT: Tumor infiltrating lymphocytes (TIL) in Epstein-Barr virus (EBV)-associated/microsatellite-unstable (MSI) gastric carcinomas (GC) constitute immune-active principal cellular components of tumor microenvironment and contribute to better prognosis. With the remarkable success of cancer immunotherapies, there is an urgent need for a comprehensive understanding of tumor-immune interactions in patients with GC in the context of host immune response. To identify GC subtype-specific immune response gene set, we tested differentially expressed genes for MSI and EBV+ GC subtypes in randomly selected test set (n = 278) in merged ACRG-SMC microarray and TCGA RNA sequencing data set. We identified Host ImmunE Response index (HIERÏ) consisting of 29 immune genes classifying GC patients into robust 3 groups with prognostic significance. Immune-high cluster 1 was enriched with PD-L1 High /EBV+/MSI/TIL High with the best clinical outcome while immune-low cluster 3 displayed worst outcome and exemplified with PD-L1 Low /EBV-/MSS. The results were validated in the same cohort (n = 279) and independent cohort (n = 181) with RNA from formalin-fixed paraffin-embedded (FFPE) tissue. Unexpectedly, nearly half of GC in cluster 1 were EBV-/MSS and 10% of cluster 3 GC were EBV+/MSI GC patients, suggesting that in addition to EBV+/MSI GC subtypes, EBV-/MSS subtype also constitutes almost half of high immune cluster and would be a good candidate for immune checkpoint inhibitor therapy. In contrary, almost 10% of EBV+/MSI GC patients may not respond to immune checkpoint inhibitor therapy. Thus, our HIERÏ gene signature demonstrates the potential to subclassify tumor immunity levels, predict prognosis and help immunotherapeutic decisions.