Immunogenomic classification of gastric cancer based on the tumor microenvironments expression of PD-L1 and CD8+ T-cell infiltration.

Authors

null

Yu Chen

Cancer Bio-immunotherapy Center, Fujian Medical University Cancer Hospital & Fujian Cancer Hospital, Fuzhou, Fujian Province, China, Fuzhou, China

Yu Chen , Gang Chen , Jia-ni Xiong , Bin Lan , Xuan Gao , Liu Jun , Jin Lin , Yaping Xu , Yan-Fang Guan , Ling Chen , Li-zhu Chen , Xuefeng Xia , Zengqing Guo

Organizations

Cancer Bio-immunotherapy Center, Fujian Medical University Cancer Hospital & Fujian Cancer Hospital, Fuzhou, Fujian Province, China, Fuzhou, China, Fujian Provincial Key Laboratory of Translational Cancer Medicine, Fuzhou, China, Department of Medical Oncology, Fujian Medical University Cancer Hospital & Fujian Cancer Hospital, Fuzhou, Fujian Province, China, Fuzhou, China, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China, Geneplus-Beijing, Beijing 102205, China, Beijing, China, Cancer Bio-immunotherapy Center & Department of Medical Oncology, Fujian Medical University Cancer Hospital & Fujian Cancer Hospital, Fuzhou, China, Fujian Cancer Hospital, Fuzhou, China, Geneplus-Beijing Institute, Beijing, China, Geneplus-Beijing Institute, Xi'an Jiaotong University, Beijing, China, Houston Methodist Research Institute, Weill Cornell School of Medicine, Houston, TX

Research Funding

No funding received
None

Background: Previous data has shown that a positive response to immunotherapy usually relies on active interactions between tumor cells and immunomodulators inside the tumor microenvironment (TME). The aim of this study was to classify gastric cancer (GC) subsets based on the TME immune status according to the expression of PD-L1 and infiltration of CD8+ T cells. Methods: One hundred and eighty-six tumor tissue from gastric cancer patients with a curative D2 gastrectomy were examined for evaluating PD-L1 and CD8+ T cells status using histopathologic analysis. The molecular characteristics of 289 GC samples in TCGA network were further analyzed to distinguish the genetic features of four immune subtypes depending on the presence of PD-L1/CD8+T cell. Results: GC samples were categorized into four types, type I (CD8+/PD-L1+, 60.3%), II (CD8-/PD-L1-, 11.8%), III (CD8-/PD-L1+, 0%), and IV (CD8+/PD-L1-, 27.9%), basing on PD-L1/CD8 expression. The PD-L1 expressing level was geographically associated with the intensity of CD8+ T cell infiltration which was significantly associated with disease-free survival (DFS) and overall survival (OS) (p = 0.003 and p = 0.006). Distinct patterns of genetic profile were described in four types of GC from TCGA database. Type I and III which PD-L1 were overly expressed had comparatively higher MSI and TMB, with EBV mainly enriched in Type I, whereas CIN was more likely to occur in PD-L1 aberrant types II and IV. SNV analysis illustrated higher gene mutations in oncogenes (PIK3CA and ERBB2), and in DNA damage repair related pathway, such as PRKDC, ATM, and SWI/SNF complexes (e.g. ARID1A) in Type I. However, TP53 mutations tend to enrich in Type II and IV. Similar results were obtained by transcriptome analysis. Conclusions: The genetic features of four immune subtypes proof that PD-L1 and CD8+ T cells status are reasonable immunogenomic classification of gastric cancer. SNV analysis prompts a potential mechanism for effectiveness of immunotherapy in Type I patients. Overall, the results may be useful for the development of clinical treatments for the blockade of immune checkpoints.

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Abstract Details

Meeting

2020 ASCO Virtual Scientific Program

Session Type

Publication Only

Session Title

Publication Only: Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary

Track

Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary

Sub Track

Esophageal or Gastric Cancer

Citation

J Clin Oncol 38: 2020 (suppl; abstr e16578)

DOI

10.1200/JCO.2020.38.15_suppl.e16578

Abstract #

e16578

Abstract Disclosures

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