Distinct tumor immune microenvironments in primary and metastatic lesions in gastric cancer patients

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This study compared the tumor immune microenvironments (TIMEs) of primary gastric cancer (PGC) and paired metastatic gastric cancer (MGC). CD4(+) and CD8(+) T-cell density and PD-L1 expression were evaluated by multiplex immunohistochemistry, DNA mismatch repair (MMR) by immunohistochemistry, and immune-related genes by RNA sequencing. Twenty-three patients who underwent surgical treatment for PGC and MGC were enrolled in this study. CD8(+) T-cell, PD-L1(+) cell, and PD-L1(+)CK(+) cell densities were significantly lower in MGC than PGC. PD-L1 positivity using a combined positive score (>= 1%) and deficient MMR were observed in 52.2% and 8.7% of PGC samples, respectively, whereas both occurred in only 4.3% of MGC samples. The most frequent TIME types were inflamed (34.8%) and adaptive immune resistance (34.8%) in PGC, and immune desert (65.2%) and immunological ignorance (73.9%) in MGC. In transcriptome analysis, the expression of the T-cell inflamed gene set and co-stimulatory gene module was down-regulated in MGC compared to PGC. The total CD8(+) T-cell density was an independent prognostic marker in both PGC and MGC (univariate P=0.002, multivariate P=0.006). Our result suggest that the TIME of metastatic tumors was less immunologically active compared to that of primary tumors in gastric cancer patients.
Publisher
NATURE PUBLISHING GROUP
Issue Date
2020-08
Language
English
Article Type
Article
Citation

SCIENTIFIC REPORTS, v.10, no.1, pp.14293

ISSN
2045-2322
DOI
10.1038/s41598-020-71340-z
URI
http://hdl.handle.net/10203/276767
Appears in Collection
MSE-Journal Papers(저널논문)
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