Open AccessCorrelation between tumor infiltrating immune cells and peripheral regulatory T cell determined using methylation analyses and its prognostic significance in resected gastric cancer
Author(s) -
Koung Jin Suh,
Jin Won Kim,
Ji Eun Kim,
Ji Hea Sung,
Jiwon Koh,
Kui Jin Kim,
Ji Won Kim,
Sang Hoon Ahn,
Do Joong Park,
HyungHo Kim,
Hye Seung Lee,
Moon Hyoung Lee
Publication year - 2021
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0252480
Subject(s) - foxp3 , hazard ratio , immune system , cd3 , medicine , cancer , cell , methylation , oncology , confidence interval , cancer research , gastroenterology , pathology , immunology , biology , cd8 , biochemistry , gene , genetics
Peripheral regulatory T cells (pTregs) are a highly immunosuppressive fraction of CD4+ T cells. We aimed to evaluate the clinical significance of pTregs in patients with gastric cancer and to determine the correlation between pTregs and immune cell infiltration in tumor microenvironment. pTregs status was determined by assessing the pTreg/total T-cell ratio (ratio of Foxp3 Treg-specific demethylated region (TSDR) to CD3G/CD3D demethylation, so-called Cellular Ratio of Immune Tolerance “ImmunoCRIT”) using methylation analyses in 433 patients with gastric cancer who received curative surgery. Among 422 evaluable patients, 230 (54.5%) had high ImmunoCRIT (> 21.0). Patients with high ImmunoCRIT had significantly shorter disease-free survival (DFS) and overall survival (OS) than those with high ImmunoCRIT ( p = 0.030, p = 0.008, respectively). In multivariate analysis, high ImmunoCRIT kept a prognostic role for shorter OS (hazard ratio [HR] 1.9, 95% confidence interval [CI] 1.4–2.9; p = 0.005). CD3+ cell density and CD4+ cell density was significantly higher within the tumor in high ImmunoCRIT group than those in low ImmunoCRIT group (CD3+ cell, 202.12/mm 2 vs . 172.2/mm 2 , p = 0.029; CD4+ cell, 56.5/mm 2 vs . 43.5/mm 2 , p = 0.007). In conclusion, the peripheral ImmunoCRIT determined by epigenetic methylation analysis provides prognostic information in resected gastric tumors.