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Distinct Tumor Immune Microenvironments in Primary and Metastatic Lesions in Gastric Cancer Patients

Authors: Seung-Myoung Son, Chang Gok Woo, Dae Hoon Kim, Hyo Yung Yun, Hongsik Kim, Hee Kyung Kim, Yaewon Yang, Jihyun Kwon, Minsuk Kwon, Tae-Yong Kim, Hyung-Don Kim, June-Young Koh, Su-Hyung Park, Eui-Cheol Shin & Hye Sook Han

Online: https://www.nature.com/articles/s41598-020-71340-z

Issue: Sci Rep. 2020 Aug 31;10(1):14293.


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.